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Interpreting the consequences of acute sleep deprivationBeerling, Wieteke

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Interpreting the consequences of acute sleep deprivation

Stress physiology as mediator

Wieteke Beerling

The resResearcBelgiumGroningScience

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Interpreting the consequences of acute sleep deprivation

Stress physiology as mediator

Proefschrift

ter verkrijging van de graad van doctor aan de Rijksuniversiteit Groningen

op gezag van de rector magnificus prof. dr. E. Sterken

en volgens besluit van het College voor Promoties.

De openbare verdediging zal plaatsvinden op

vrijdag 5 september 2014 om 16.15 uur

door

Wieteke Beerling

geboren op 15 januari 1983 te Smallingerland

Promotor

Prof. dr. J.M. Koolhaas

Copromotores

Dr. W.H.I.M. Drinkenburg

Dr. P. Meerlo

Beoordelingscommissie

Prof. dr. D.G.M. Beersma

Prof. dr. G. van Dijk

Prof. dr. D. Kalsbeek

Table of contents

Chapter 1: General Introduction .............................................................................. 7

Chapter 2: Physiological and hormonal responses to novelty exposure in rats are mainly related to ongoing behavioural activity ........................................................ 25

Chapter 3: Simultaneous assessment of behavioural, physiological and hormonal responses to acute gentle handling sleep deprivation in rats ................................. 51

Chapter 4: Short sleep deprivation by gentle handling is a mild activator of the stress systems but does not affect the subsequent response to novelty exposure 69

Chapter 5: Sleep-deprived rats have normal behavioural and physiological responses to frustrative non-reward stress ............................................................ 95

Chapter 6: Attentional and physiological aspects measured in the 5-choice serial reaction time task are unaffected by acute sleep deprivation in rats .................... 117

Chapter 7: General Discussion ............................................................................ 143

Reference List .................................................................................................... 165

Nederlandse samenvatting ............................................................................... 181

Dankwoord ......................................................................................................... 191

Curriculum Vitae ................................................................................................ 197

List of publications ........................................................................................... 198

Chapter 1

General Introduction

Chapter

8

SLEEP

Even t

around

function

increas

and Ar

averag

become

Rajarat

problem

Animal

resting

2009).

sleep u

though

further

S

and ne

determ

eye-mo

NREM

stages

sleep s

with sh

hard to

al., 20

(Bening

2012).

O

The ma

regulat

Berger

r 1

P AND SLE

hough the

one third

ns. In toda

sed social

rand, 1995

e time per

e common

tnam and

m in today’

s with co

phase, wh

Sleep imp

unless sle

t to be im

understan

Sleep is a

eurochemic

ine the ex

ovement (

sleep can

of sleep (B

stages a n

horter sleep

o distinguis

012). The

gton and H

One of the

aintenance

ion and de

, 1980; M

EEP SHOR

e exact fun

d of their

ay’s societ

pressures

5; Hublin e

r day spen

n in today’

Arendt, 20

’s society.

mplex ner

hich are co

poses a s

eep has a

portant for

nding the co

a complex

cal change

xact functio

NREM) sl

n be subdiv

Brown et a

umber of t

p durations

sh the 3 NR

different

Heller, 199

e main hyp

e of brain

etoxification

McGinty an

RTAGE

nction of s

entire life

y, with our

, more peo

et al., 2001

nt asleep h

’s society

001). Slee

Animals a

rvous stru

omparable

substantial

n importan

r humans

onsequenc

non-homo

es that fol

on of sleep

eep and

vided into 3

al., 2012). D

times. In r

s but with

REM sleep

sleep sta

5; Siegel,

potheses s

homeosta

n have bee

nd Szymus

sleep is un

e sleeping

r modern l

ople deal w

1; Rajaratn

has decrea

(Bonnet a

p deprivat

also show c

ctures sho

to human

risk to an

nt function

but also fo

ces of slee

ogenous p

low a cycl

p. Sleep co

REM (RE

3 stages th

During slee

rats, sleep

in total aro

p stages (B

ages are

1995; Wal

states that

tic process

en suggest

siak, 1990

nknown, th

g suggests

lifestyle of

with regula

nam and A

ased, also

and Arand,

tion is ther

cycles of b

ow sleep-

sleep (Hor

nimals, the

n (Horne,

or many a

ep deprivat

phenomeno

lic pattern

onsists of

M) sleep

hat corresp

ep, most h

is more fr

ound 12 h

Borbely an

thought t

ker and St

sleep serv

ses like en

ted as a fu

0; Inoue e

he fact tha

s that slee

around th

ar sleep de

Arendt, 20

disrupted

, 1995; Hu

refore con

behavioura

like condit

rne, 2002;

erefore an

2002). Th

animals. Th

tion and fo

on with ele

. This mak

two main

that altern

pond to inc

humans wil

ragmented

of sleep e

d Neuhaus

to have s

tickgold, 2

ves a hom

nergy bala

unction of s

t al., 1995

at humans

ep has im

he clock wo

eprivation (

001). Not o

normal sle

ublin et al.

sidered a

al rest and

tions durin

Vassalli a

nimals sho

herefore, s

his thesis

cused on r

ectrophysi

kes it com

states; no

nate. In h

creasingly

l cycle tho

d than in h

each day, a

s, 1979; B

specific fu

004; Brow

meostatic fu

ance, temp

sleep (Wal

5; Maquet

s spend

mportant

ork and

(Bonnet

only the

eep has

., 2001;

serious

activity.

ng their

nd Dijk,

ould not

sleep is

aims at

rats.

ological

mplex to

n-rapid-

humans,

deeper

ough the

humans,

and it is

Brown et

unctions

wn et al.,

unction.

perature

ker and

t, 1995;

Brown

plastici

et al., 2

2009; B

consoli

importa

informa

et al., 2

2004; B

importa

and mo

and Be

Cirelli,

presen

potenta

their c

potenta

sleep s

weaken

homeo

depriva

affectin

Vgontz

2012).

stores

corticot

D

loss st

function

sleep d

1999; A

Kamero

shortag

et al., 20

ty, which is

2001; Ellen

Brown et a

dation of

ant for the

ation proce

2001; Peig

Brown et a

ant for hig

otor contro

enington, 2

NREM sle

t during w

ation result

connection

ation reduc

serves to

n the sy

stasis may

ation studi

ng metabo

zas et al.,

For exam

(Beningto

trophin-rele

Despite th

tudies hav

ning. Epid

disorders,

Ayas et al.

ow, 1989;

ge is most

12). Sleep

s crucial fo

nbogen et

al., 2012). E

explicit, e

consolida

essing and

neux et al.

al., 2012).

her execut

ol (Bonnet

2006; Brow

eep prima

waking ind

ts in an in

ns (Tonon

ces the av

downscal

ynaptic c

y affect lea

es indicat

olic, endoc

1999; Vgo

mple, NRE

n and He

easing hor

he fact tha

ve shown

emiologica

such as i

., 2003; Ga

Chang et

strongly a

p is also t

or learning

al., 2006;

Existing lite

episodic m

ation of pro

storage (K

., 2001; Be

Sleep dep

tive functio

, 1985; M

wn et al., 20

arily serves

uces syna

crease in t

ni and C

vailable sp

e the syn

connection

arning, me

e that sle

crine and

ontzas et a

EM sleep i

ller, 1995)

rmone regu

t the exac

that sleep

al studies

nsomnia,

angwisch e

al., 1997;

associated

thought to

and mem

Walker a

erature sug

memory w

ocedural m

Karni et al.

enington an

privation s

ons of the

aquet, 200

012). Acco

s synaptic

aptic poten

the streng

Cirelli, 200

pace and

naptic stre

ns. Distur

mory perfo

eep is invo

immunolo

al., 2004; G

is importa

) and grow

ulate NREM

ct function

p is impor

show cor

with cardi

et al., 2006

Riemann e

with impai

contribute

ory proces

nd Stickgo

ggests tha

whereas RE

memory an

, 1994; Pli

nd Frank, 2

studies hav

brain com

01; Durme

ording to th

homeosta

ntation. Th

th, size an

06). This

energy res

ength to lo

rbances

ormance a

olved in p

gical syste

Gangwisch

nt in the

wth hormo

M sleep (S

of sleep r

rtant for p

rrelations o

ovascular

6) and psy

et al., 2001

irments of

Ge

e to neuro

sses (Maqu

old, 2006;

at NREM sl

EM sleep

nd some ty

hal and Bo

2003; Walk

ve also sh

mpromising

er and Din

he hypothe

asis. High

he waking-

nd number

waking-i

serves in

ower ener

in sleep-

and mood.

peripheral

ems (Spie

h et al., 20

replenishm

one-releasi

Schussler e

remains hy

proper phy

of habitual

disorders

ychiatric di

1). In huma

mood, cog

eneral Intro

onal and s

uet, 2001;

Vassalli a

leep is invo

is though

ypes of em

orn, 1999;

ker and St

own that s

g mood, co

ges, 2005

esis of Ton

neuronal

-induced s

r of synaps

nduced s

the brain.

rgy levels

-related s

In addition

functions

egel et al.

006; Brown

ment of g

ing hormo

et al., 2006

ypothetica

ysical and

l short sle

(Schwartz

seases (Fo

ans, chron

gnitive func

oduction

9

synaptic

Graves

nd Dijk,

olved in

ht to be

motional

Graves

ickgold,

sleep is

ognition

5; Frank

noni and

activity

synaptic

ses and

synaptic

NREM

and to

synaptic

n, sleep

thereby

, 1999;

n et al.,

lycogen

one and

6).

al, sleep

mental

eep and

z et al.,

ord and

ic sleep

ctioning

Chapter

10

and mo

et al., 2

N

mecha

hypothe

the str

hypothe

sleep lo

SLEEP

The sy

adreno

respon

Sleep d

Higher

during

1999).

neuron

(Axelro

sympat

release

noradre

Activat

Cortico

activati

energy

of the h

to the m

the rel

r 1

otor perform

2003).

Not only t

nisms und

eses have

ress syste

esis that t

oss in rats

P DEPRIVA

ympathetic

ocortical (H

se and are

deprivatio

catechola

sleep dep

The SAM

s that trigg

od and Re

thetic nerv

e of norad

energic ce

ion of the

otrophin-Re

on (Koob

needed to

heart and b

muscles a

eased adr

mance (Pi

the functio

erlying the

e been pro

ms. There

he stress

.

ATION AN

c-adrenom

HPA) axis

e both affec

on and the

mine level

privation (L

M system a

ger the rele

eisine, 19

vous system

drenalin (A

ll clusters

ese norad

eleasing-H

, 1999). T

o cope wit

by increasi

nd an incr

renalin aff

lcher and H

on of sleep

e adverse e

oposed. On

efore, the

systems a

ND THE ST

edullary (

are consi

cted by sle

e SAM sys

ls, indicativ

Lusardi et

acts via tw

ease of ad

84; Johns

m, which i

Axelrod an

in the brain

renergic n

ormones

The relea

h the stres

ing blood p

reased me

fects the g

Huffcutt, 1

p needs f

effects of s

ne of such

focus of

are the cor

TRESS SY

SAM) sys

dered to b

eep depriva

stem

ve of SAM

al., 1996;

wo differen

drenalin fro

son et al.

nnervates

nd Reisine

n stem are

neurons d

(CRH) th

ased adren

ssor. They

pressure. T

tabolic rate

glucose m

996; Dinge

urther clar

sleep loss

hypothes

this thesis

re mediato

YSTEMS

stem and

be the two

ation.

M system a

Tochikub

t pathways

om the adr

, 1992). T

many orga

e, 1984; J

e the basis

uring stres

hat are re

nalin and

achieve th

This results

e (Leal-Ce

metabolism

es et al., 1

rification, a

remain spe

es sugges

s is to fu

ors of the a

the hypot

o key play

activation,

bo et al., 1

s. One pa

renal medu

The other

ans in the

Johnson e

for the sym

ss is part

eleased d

noradrena

his by incr

s in an inc

erro et al.,

m thereby

997; Van D

also many

eculative.

sts involve

rther expl

adverse ef

thalamic-p

yers in the

have bee

1996; Irwin

thway con

ulla into th

r pathway

body thro

t al., 1992

mpathetic o

tly depend

during HP

alin mobil

reasing the

reased blo

2003). Mo

causing n

Dongen

y of the

Several

ment of

ore the

ffects of

pituitary-

e stress

n found

n et al.,

nsists of

e blood

is the

ugh the

2). The

outflow.

dent on

PA axis

ize the

e output

ood flow

oreover,

nutrients

stored

1984; J

O

catecho

day wit

De Boe

catecho

Irwin et

increas

accomp

Tochiku

shown

rate an

sympat

signific

1979; C

T

activati

sugges

and dis

1991; I

result i

Conseq

chronic

fatigue

recove

stay el

initiatin

sympat

agreem

hyperte

T

sympat

in the mu

Johnson et

One woul

olamine le

th lower lev

er and van

olamines t

t al., 1999

se in catec

panied by

ubo et al.,

to be asso

nd blood pr

thetic activ

ant sympa

Chen, 1991

These diffe

on is high

sts that the

scontinuity

rwin et al.

in a state

quently, al

cally restric

may lead

ry after ac

evated (Lu

g and ma

thetic activ

ment with a

ension and

The activi

thetic acti

scles to be

t al., 1992;

d expect

evels as ad

vels during

der Gugte

that are m

). Most stu

cholamine

increases

1996; Irw

ociated wit

ressure (Sf

vation in

athetic act

1).

erences ca

ly depende

e extent of

y of sleep

, 1999; Tie

of fatigue

so sympat

cted or di

to increas

cute sleep

usardi et

aintaining

vation (Be

a study sho

d cardiovas

ities durin

vation. Sy

ecome ava

Leal-Cerr

sleep de

drenalin an

g the circad

en, 1987).

aintained l

udies show

levels tow

s in heart

win et al.,

h sympath

forza et al.

response

tivation af

an be expl

ent on the

f sympathe

rather tha

emeier et a

e with dec

thetic activ

isrupted s

sed sympa

deprivatio

al., 1996;

wakefulne

rgmann et

owing that

scular dise

ng sleep

ympathetic

ailable to

ro et al., 20

privation t

nd noradre

dian sleep

Sleep ons

low during

wed that sl

wards leve

rate and

1999). Eve

hetic activa

., 2004). D

to sleep

fter sleep

lained by t

e method o

etic activat

an to the

al., 2002).

creased ar

vity is redu

leep not a

thetic activ

on is insuff

Tochikubo

ess in a

t al., 1989;

chronic sl

ases (Gan

deprivation

c activatio

provide en

003).

to be ass

enalin leve

p phase (Ak

et is assoc

g sleep (Ak

leep depriv

els seen d

blood pres

en brief aw

ation and w

Despite the

deprivation

deprivatio

the fact tha

of sleep de

tion is mai

duration o

Prolonged

rousal, ale

uced (Meer

associated

vation. Stu

ficient, hea

o et al., 1

state of s

Everson e

eep restric

ngwisch et

n also hig

on is depe

Ge

nergy (Axe

sociated w

els vary wit

kerstedt an

ciated with

kerstedt an

vation is a

during wak

ssure (Lus

wakenings

with a temp

fact that m

n, some s

on (Akerste

at the exte

eprivation.

nly related

of sleep d

d total slee

ertness an

rlo et al., 2

d with the

udies have

art rate an

996). It i

sleep debt

et al., 1989

ction is an

al., 2006).

ghly affec

endent on

eneral Intro

elrod and R

with increa

th the time

nd Froberg

a rapid de

nd Froberg

associated

kefulness.

sardi et al.

s from slee

porary rise

most studie

studies re

edt and F

ent of symp

Existing lit

d to the dis

eprivation

ep depriva

d mental

2008). In c

same de

shown tha

nd blood p

is suggest

t requires

9a). This is

increased

.

ct the deg

n the amo

oduction

11

Reisine,

ases in

e of the

g, 1979;

ecline in

g, 1979;

with an

This is

., 1996;

ep have

in heart

es show

port no

Froberg,

pathetic

terature

sruption

(Chen,

tion will

activity.

contrast,

gree of

at when

pressure

ted that

higher

s also in

risk for

gree of

ount of

Chapter

12

physica

Studies

depriva

not req

studies

sleep d

Meerlo

Sleep d

Severa

with m

et al., 1

rodents

et al., 1

al., 200

when e

adrena

et al., 1

al., 200

H

hypotha

Vasopr

results

bloodst

in the b

1984; J

is the s

known

Johnso

system

that ac

produc

r 1

al activity,

s that rep

ation often

quire muc

s where org

deprivation

et al., 200

deprivatio

al studies i

ildly elevat

1980; von

s, sleep de

1983; Such

06). These

exposed to

al (HPA) ax

1999; Chap

08).

HPA axis

alamus th

ressin upo

in the

tream. In t

blood; cort

Johnson et

supply of

to regulat

on et al., 1

m is well re

ct back on

tion, preve

emotiona

port no o

concern s

ch emotion

ganisms h

n period s

08).

on and the

n healthy s

ted plasma

Treuer et

eprivation i

hecki et al.

increases

o a stresso

xis activati

potot et al.

activation

hat secret

on stimulat

release o

turn, ACTH

tisol in hum

t al., 1992

energy by

te a variety

992; Sapo

egulated. A

the hypoth

ents chron

al arousal

or low inc

studies wh

nal or cog

ave to ma

showed hig

e HPA axis

subjects s

a levels of

al., 1996;

s associat

, 1998; Me

s are consi

or. The ele

ion (von Tr

, 2001; Hip

is regulate

tes the C

tion. Thes

of the ad

H stimulate

mans and

). One of

y convertin

y of other

olsky et al

A negative

halamus a

nically ele

and cogn

creases in

here organ

gnitive dem

intain alert

gher symp

s

howed tha

f the adren

Spiegel e

ed with a m

eerlo et al.

dered as m

evations ar

reuer et al

polide et a

ed by the

Corticotrop

e peptides

drenocortic

es the adr

corticoster

the main e

ng proteins

processes

., 2000; Le

e feedback

and pituitar

vated con

nitive dem

n sympath

isms are in

mand. In

tness and

pathetic ac

at sleep de

nocortical h

et al., 1999

mild increa

, 2002; Hip

mild when

re indicativ

., 1996; Su

al., 2006; S

paraventr

phin-Releas

s stimulate

cotropic h

enal cortex

rone in rod

effects of t

s to glucos

s as well (

eal-Cerro e

k system c

ry gland to

ncentration

and (Mee

hetic activ

n a relaxe

contrast,

d have to p

ctivity (Zho

eprivation i

hormone c

9; Chapoto

ase in corti

polide et a

compared

ve of hypot

uchecki et

Sgoifo et al

icular nucl

sing-Horm

e the pitu

ormone (

x to releas

dents (Axe

the release

se. The gl

Axelrod an

et al., 200

consisting

o suppress

s of gluco

erlo et al.,

vity during

d position

sleep dep

perform du

ong et al.

s also ass

cortisol (Ak

ot et al., 20

costerone

l., 2006; S

to levels r

thalamic-p

al., 1998;

., 2006; M

leus (PVN

mone (CRH

itary gland

(ACTH) in

se glucoco

elrod and R

ed glucoco

lucocortico

nd Reisine

3). The HP

of glucoco

s CRH and

ocorticoids

2008).

g sleep

and do

privation

ring the

, 2005;

sociated

kerstedt

001). In

(Tobler

Sgoifo et

reached

pituitary-

Spiegel

eerlo et

) of the

H) and

d which

nto the

orticoids

Reisine,

orticoids

oids are

e, 1984;

PA axis

orticoids

d ACTH

s in the

blood (

1997).

the bra

(Dinan,

brain st

activate

1999).

H

suprac

change

Glucoc

before

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ent in the

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cocorticoid

affen et al.,

ods used

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nitive dem

olsky, 199

eives regul

nergic syst

d Herman

ystem toge

tivity, which

ormally dis

of the hy

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ping phase

ubstrates

p deprivat

ng sleep a

ated cortis

th-Schwalb

evels durin

p (Meerlo e

nic activati

n light of

and prolo

chatzberg,

cortisol leve

evening fo

mechanism

es showin

deprivation

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, 1983; Fo

to induce

ependent

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1; Johnso

atory inpu

tem and th

, 2009). F

ether form

h in turn a

splays a d

ypothalamu

erone and

early in the

. This peak

(Weitzma

tion is ther

as compar

sol levels d

be et al.,

ng sleep

et al., 2002

on of the H

the devel

onged elev

, 2005). So

els during

ollowing sle

ms behind th

ng mild in

, some stu

uring acute

ollenius et

sleep dep

on the am

g the perio

n et al., 1

uts from th

he bed nu

Furthermor

a feed-for

ctivates fo

daily rhyth

us and is

ACTH (M

e resting p

k prepares

n et al.,

refore not

red to duri

during aro

1991; E

deprivatio

2; Sgoifo e

HPA axis is

lopment o

vated cort

ome huma

recovery in

eep depriv

his recurre

ncreases

udies show

e sleep de

al., 1992).

privation. A

mount of

od of sleep

Ge

992; Herm

he hippoca

cleus of th

re, the CR

rward syste

orebrain CR

m that is

s characte

Moore and

phase and

s the body

1971). T

surprising

ing wakefu

usal from

Ekstedt et

n disappe

et al., 2006

s thought t

of mood d

isol levels

an studies

n healthy s

vation (Lep

ent activatio

in glucoco

wed no ch

eprivation

. These dif

After all, th

physical a

p deprivati

eneral Intro

man and C

ampus, am

he stria te

H system

em whereb

RH activity

controlled

erized by

d Eichler,

show a pe

for awake

The incre

as glucoc

ulness. Stu

sleep and

al., 2004

ear rapidly

6). When re

to occur. T

disorders a

are hallm

also show

subjects, e

proult et al

on are unk

orticoid le

hanges or

(Akerstedt

fferences

he extend

activity, em

on (Meerlo

oduction

13

Cullinan,

mygdala,

rminalis

and the

by CRH

y (Koob,

by the

parallel

1972).

eak just

ening by

ease in

corticoid

udies in

d during

4). The

y during

ecovery

This has

as both

marks of

ed, that

elevated

., 1997;

known.

evels in

even a

t et al.,

may be

of HPA

motional

o et al.,

Chapter

14

2008).

activity

Rechts

levels m

or psyc

Adapti

The ac

the org

energy

al., 20

enhanc

increas

Quirart

and S

appreh

the imm

prepare

1999;

reduce

axis an

that are

al., 200

D

stress

concen

particu

Also,

hippoca

2009).

wide r

immuno

r 1

Higher HP

or face a

schaffen et

may be ob

chologically

ve and ma

cute stress

ganism to d

to the bo

003), they

cement of

se in behav

te et al., 1

Seeman,

ension an

mune syst

es for poss

Heinz et a

d (Heinz e

nd SAM sy

e in a rang

01).

Despite the

systems

ntrations o

larly in the

conditions

ampal vol

Moreover

range of s

odeficiency

PA axis ac

cognitive

t al., 1999

bserved du

y active an

aladaptive

response

deal with a

dy (Axelro

also act

learning,

vioural res

1997; Arns

1999; Mc

d fear are

tem is affe

sible infect

al., 2003).

et al., 2003

ystem func

ge that is p

e adaptive

is not co

of stress

e hippocam

with hig

ume and

, chronic s

stress rela

y and ca

ctivation is

challenge

9; Chapoto

uring sleep

nd are high

e consequ

is general

a situation.

od and Rei

on the h

enhancem

ponsivene

sten, 1998

cEwen, 1

initiated b

ected; imm

tion or inju

Furtherm

3). Regula

ction and

protective f

e functions

onsidered

hormones

mpus (Sap

gh glucoc

cognitive

stress sys

ated disor

ardiovascu

s observed

e (Radoms

ot et al., 2

deprivatio

hly fatigued

uences

ly conside

The relea

isine, 1984

hippocamp

ment of m

ess and ale

8; Arnsten

999a; Mc

by stress h

mune cells

ry (Khansa

more, the s

ar sleep is

to maintai

for the bra

of the stre

to be ad

s promote

polsky and

corticoid le

impairme

stem activa

rders such

lar disord

d when org

ki et al., 1

2001). In c

on if organ

d.

red to be h

sed stress

4; Johnson

pus and a

memory for

ertness (Mc

and Gold

cEwen, 1

ormones (

redistribut

ari et al., 1

secretion o

thought to

in stress h

ain (Abraha

ess respon

daptive. F

s neurona

Pulsinelli,

evels are

ents (Sapo

ation is co

h as dep

ers (McE

ganisms en

992; Chap

contrast, lo

isms are n

highly adap

s hormones

n et al., 19

amygdala

r emotiona

cEwen and

man-Rakic

1999b). A

(Lazarus, 1

te and the

990; McEw

of sex ste

o contribut

hormones

am et al., 1

nse, chroni

requent e

al damage

1985; So

e associat

olsky, 200

onsidered t

ression, a

wen, 199

ngage in p

potot et al

ow cortico

not physiol

ptive and a

s provide n

992; Leal-C

thereby c

al stimuli

d Sapolsky

c, 1998; M

Also, feeli

1993). In a

e immune

wen and S

roid horm

te to norm

at concen

1997; Abra

c activatio

exposure t

e and ce

ousa et al.,

ted with

00; Huang

to contribu

anxiety dis

98; McEwe

physical

., 1998;

osterone

ogically

allowing

not only

Cerro et

causing

and an

y, 1995;

McEwen

ngs of

addition,

system

eeman,

ones is

mal HPA

ntrations

aham et

n of the

to high

ell loss,

, 1999).

smaller

et al.,

ute to a

sorders,

en and

Seema

depriva

respon

Sleep d

The stu

comple

classica

implies

conseq

serious

the no

concep

respon

homeo

regain

discuss

but are

2009; K

should

process

1991; L

respon

stimulu

H

hormon

experie

the clas

stimuli

these s

conditio

conside

an, 1999;

ation caus

sible for so

deprivatio

udies revie

ete depriva

al neuroe

s that slee

quences of

s conceptu

n-specific

pt was lat

se. Curre

stasis and

homeosta

sions as m

e not stres

Koolhaas

be consi

sing of the

Levine, 20

se is an

us is in gen

However,

nal activati

ence of ave

ssical neu

but some

systems a

on that

erable part

Korte et

ses chron

ome of the

on as a str

ewed in the

ation of sl

ndocrine s

ep depriva

f sleep dep

al problem

response

ter refined

ently, a st

d the stres

asis (Chro

many activit

ssful (Levi

et al., 201

idered as

e stimulus

005). This

indicator

neral consid

stress sh

on of the s

ersion (Ko

roendocrin

etimes also

re crucial

requires

t of the ph

al., 2005

ic or alte

e adverse e

ressor

e previous

eep is as

stress sys

ation cons

privation. T

m in stress

of the bo

d by distin

tressor is

ss respons

ousos, 200

ties of an

ne, 1991;

11). Levine

a proces

and the b

has led to

of a stres

dered stres

hould not

stress syst

olhaas et a

ne stress s

o in respo

for mobiliz

or cause

hysiologica

5). In this

ered stress

effects ass

sections i

sociated w

stems. An

stitutes a

This is not

research.

ody to a n

nguishing

consider

se is cons

09). This

organism

McEwen,

e and Urs

ss that in

behavioura

o the gene

ssful situa

ssful when

only be i

tems. It sho

al., 2011).

systems no

onse to po

zation of e

es behav

al and horm

s thesis w

s system

ociated wit

ndicate tha

with at lea

importan

stressor t

a trivial is

Hans Sely

noxious st

between

red a stim

idered a r

concept o

relate to m

1998; Le

sine empha

cludes the

al and phy

eral view t

ation (Arm

n the stress

nterpreted

ould also b

The proble

ot only occ

ositive and

energy and

ioural act

monal resp

Ge

we hypoth

activation

th sleep de

at disturba

ast a mild

t question

that media

sue since

ye defined

timulus (S

a stresso

mulus tha

reaction of

of stress h

maintenanc

evine, 2005

asized the

e stimulus

ysiological

that occur

mario, 200

s systems

d as the p

be interpre

em here is

curs in resp

d rewardin

d are thus

tivation. C

ponses to a

eneral Intro

hesise tha

n that in

eprivation.

ance, restri

activation

n is wheth

ates the a

it touches

stress in 1

elye, 1950

r and the

t is a th

f the orga

has led to

ce of home

5; Romero

e view that

s, the per

response(

rence of a

06). There

are activat

physiologic

ted as a co

s that activ

ponse to a

g stimuli.

s activated

Conseque

a certain s

oduction

15

t sleep

turn is

ction or

n of the

her this

adverse

upon a

1950 as

0). This

e stress

hreat to

nism to

o many

eostasis

o et al.,

t stress

rceptual

(Levine,

a stress

efore, a

ted.

cal and

ognitive

vation of

aversive

In fact,

d in any

ntly, a

situation

Chapter

16

can be

behavio

(Koolha

as a co

discuss

hypothe

unified

arousa

SAM s

situatio

water

respon

defeat

Bonilla-

reward

not be

the stu

aversiv

Weiss

stimulu

and/or

I

and in

rodent

with be

system

proced

when s

the act

wakefu

r 1

e a direc

oural activ

aas et al.,

omponent

sed these

esis; they

system of

l level (He

system an

ons but als

reward, se

ses that a

(Schuurm

-Jaime et

ing and co

considere

udies that

ve stressor

already sh

us that ind

controlled

In order to

order to in

studies ar

ehaviour an

ms in man

ures. We

stress syst

tivity of the

ulness.

ct reflectio

vity, rather

2011). He

of the gen

concepts

suggest th

f arousal a

ennessy a

nd HPA a

so to rewar

exual beh

are similar

an, 1980;

al., 2006

ontrollable

d an avers

show that

r (Schuurm

howed in 1

uces stres

(Weiss, 19

o determin

nterpret th

re needed

nd should r

ny studies

hypothesi

tem activat

e stress sy

on of the

r than a re

ennessy an

neral arous

of stress

hat the HP

nd that HP

and Levine

axis activa

rding, cont

aviour and

r in magn

Bronson

6; Koolhaa

situations

sive stress

t uncontrol

man, 1980;

1972 that

ss patholog

972).

e to what

e consequ

that shou

reduce stre

s may be

ze that sl

tion dissoc

ystems rea

metabolic

eflection o

nd Levine

sal system

s and arou

PA axis can

PA axis res

e, 1979). T

ation in re

trollable sit

d winning

nitude as

and Desja

as et al., 2

activate th

sful situatio

llability is

Muir and

it is not th

gy but the

degree sle

uences of

ld study th

ess confou

the resu

eep depriv

ciates from

aches leve

c requirem

of the ave

already re

m (Henness

usal in te

n be consi

sponses ar

This is con

esponse t

tuations. S

a social

highly ave

ardins, 198

2011; Buw

he SAM an

on. In line w

one of the

Pfister, 19

he physiolo

e degree in

eep depriv

sleep dep

he stress s

unding effe

ult of arte

vation can

m the beha

els beyond

ments for

rsive natu

ecognized t

sy and Lev

rms of a

idered as a

re a reflect

nfirmed by

to aversiv

Studies sho

interaction

ersive situ

82; De Bo

walda et a

nd HPA sy

with these

e main pro

986; De Bo

ogical natu

n which it

vation cons

rivation co

system act

ects. The a

efacts of

n be cons

avioural res

d those see

normal o

ure of a co

the stress

vine, 1979

psychoen

a compone

tion of cha

y studies s

ve, uncont

owed that

n elicit HP

ations like

oer et al.,

al., 2012).

ystems but

e observati

operties of

oer et al.,

ure of an a

can be pr

stitutes a s

orrectly, co

tivation in

activation o

the exper

idered a s

sponse an

en during

ongoing

ondition

system

9). They

ndocrine

ent of a

anges in

showing

trollable

food or

PA axis

e social

1990a;

These

t should

ons are

f a true

1990a).

aversive

redicted

stressor

ontrolled

concert

of stress

rimental

stressor

nd when

relaxed

SLEEP

Sleep d

also af

under

subject

et al., 2

acute s

a subse

sleep d

h of sle

brief re

2006;

signific

These

accumu

a sligh

respon

induced

affectin

sleep r

increas

T

measu

depriva

Symon

sleep d

challen

have b

exercis

1984; M

respon

2005).

P DEPRIVA

deprivation

ffect the re

strictly con

ts are facin

2008). A f

sleep depr

equent str

deprivation

eep depriv

estraint or

Novati et

antly dam

findings to

ulate over

htly differe

sivity. Suc

d higher

ng the ACT

restriction s

sed relative

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red the ph

ation (Mart

s et al., 19

deprivation

nge. The c

been affec

se after sle

Martin et a

siveness

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ATION AN

n may not o

esponsivity

ntrolled sti

ng new cha

few contro

ivation for

essor (Me

n (i.e., 48 h

vation per d

r inescapa

al., 2008

mpened, th

ogether sug

time (Mee

nt effect

checki and

corticoster

TH respon

studies is

e to the pit

also a limi

hysiologica

tin and Che

988; Martin

n on the ac

cognitive a

ted since

eep depriv

al., 1986).

to work-re

nd co-wor

ND STRESS

only affect

y of these

imulus-poo

allenges o

olled roden

less than

erlo et al.,

h of total sl

day for a w

able foot s

8). Particul

he adrenal

ggest that

erlo et al., 2

of chronic

d co-worke

rone level

se (Suche

that in bot

uitary ACT

ited numb

l response

en, 1984; M

n, 1988). M

cute physi

and emotio

a reduced

ation has

Another s

elated cha

rkers sugg

S REACTI

the basal

systems to

or conditio

or stressors

nt studies h

a day doe

2002; Nov

leep depriv

week or m

hock in ra

larly, while

l corticoste

the effect

2002; Nova

c REM sle

ers showed

ls after e

ecki et al.,

th cases th

TH respons

er of cont

es to mild a

McMurray

Most of thos

iological a

onal perce

d perceive

been repo

study show

allenges a

gested tha

IVITY

activity of

o challeng

ons but wi

s on top of

have been

es not affec

vati et al.,

vation) or

more) alters

ats (Meerlo

e the pitu

erone resp

of sleep lo

ati et al., 20

eep depriv

d that 96 h

xposure t

2002). Th

he adrenal

se.

trolled hum

and high in

and Brow

se studies

nd hormon

ption of th

ed exertion

orted (Mart

wed reduc

fter sleep

t even if

Ge

the stress

ges. This w

ll become

f the depriv

n done. Th

ct the HPA

2008). Ho

chronic sle

s the HPA

o et al., 20

uitary ACT

ponse rem

oss on stre

008). Anot

vation on

h of REM

to a mild

e similarity

l corticoste

man studie

ntensity ex

n, 1984; M

showed no

nal respon

his challen

n and tole

tin, 1981;

ced cognitiv

deprivatio

sleep dep

eneral Intro

systems b

will not be

noticeable

ved sleep

hese sugg

A axis resp

owever, pro

eep restric

A axis resp

002; Sgoifo

TH respon

mained un

ess reactiv

ther study s

stress HP

sleep dep

stressor

y with the

erone resp

es. Some

xercise afte

Martin et al

o serious e

nses to a p

nge may h

rance of p

Martin and

ve and em

on (Zohar

privation do

oduction

17

but may

evident

e when

(Meerlo

est that

ponse to

olonged

tion (20

onse to

o et al.,

se was

altered.

vity may

showed

PA axis

privation

without

chronic

ponse is

studies

er sleep

., 1986;

effect of

physical

however

physical

d Chen,

motional

r et al.,

oes not

Chapter

18

affect t

indirect

changin

2008).

I

conditio

stress r

SLEEP

In hum

of slee

to impa

stimuli

stimuli

2001).

truck d

conseq

2008).

W

these h

but mo

comple

attentio

control

Dinges

(Harriso

1992),

depriva

et al.,

hormon

affect b

Sapols

r 1

the respon

tly by alte

ng the aff

In this the

ons wheth

response t

P DEPRIVA

mans, reduc

p loss and

airments in

(Jewett et

with a hig

Sleepines

drivers and

quences (H

While man

have found

ore a term

ex to det

onal deficit

processe

s, 2005), s

on and Ho

without a

ation has d

2006). S

nes do no

brain func

ky, 1995;

nsiveness

ering the p

ferent inpu

esis we aim

her sleep d

to a challen

ATION AN

ctions in s

d sleepines

n sustained

al., 1999;

gher sustai

ss is comm

d has show

Haraldsson

ny attempts

d to be com

m for seve

ermine th

ts resulting

es that rel

such as at

orne, 1999)

affecting a

different eff

Studies als

ot only sup

ctioning, at

Quirarte e

of the ne

perception

uts to the

med to st

deprivation

nging situa

ND ATTENT

ustained a

ss. Studies

d attention

Johnsen e

ined and s

monly obse

wn to lead

n et al.,

s have bee

mplex. The

eral differe

he underly

g from sle

ly on the

ttention to

) and cogn

aspects of

fects on th

so sugges

pport meta

ttentional p

et al., 1997

euroendoc

of certain

neuroendo

udy in mo

n, by actin

ation.

TIONAL F

and selectiv

s showed t

tasks that

et al., 2002

selective a

erved amo

d to atten

1990; Din

en made to

e fact that a

ent varietie

ying mech

eep loss r

prefrontal

relevant c

nitive perse

executive

he underlyi

st involvem

abolic proc

processes

7; Arnsten

crine syste

n stimuli o

ocrine con

ore detail a

ng on the

FUNCTION

ve attentio

that a sing

t require at

2; Van Don

attentional

ong nurses

tion proble

ges, 1995

o unravel t

attention is

es of atten

hanisms.

eflect a dy

l cortex (N

cues (Nort

everation (H

e function.

ng mecha

ment of th

cesses an

, cognition

n, 1998; Ar

ems direct

on a cogni

ntrol region

and under

stress sys

NING

on are amo

gle night of

ttention to

ngen et al.,

demand (

s, air traff

ems that c

5; Caldwe

the underly

s not a uni

ntional pro

Studies s

ysregulatio

Norton, 19

ton, 1970)

Horne, 198

. This ind

nisms of a

he stress

d physical

n and moo

rnsten and

tly, it may

tive level

ns (Meerlo

r non-conf

stems, affe

ong the firs

f sleep los

auditory o

, 2003) but

Drummond

fic controlle

can have

ll, 2001; R

ying mecha

tary pheno

ocesses m

suggest th

on of beha

970; Durm

), flexible t

88; Wimme

icates tha

attention (C

systems.

l activity b

od (McEw

d Goldman

y do so

and by

o et al.,

founded

ects the

st signs

ss leads

or visual

t also to

d et al.,

ers and

serious

Rogers,

anisms,

omenon

makes it

hat the

avioural

mer and

thinking

er et al.,

at sleep

Cordova

Stress

but also

wen and

n-Rakic,

1998; M

sleep lo

are inv

Therefo

attentio

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a beha

et al., 2

affects

thesis

affects

activati

AIM AN

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physica

remain

effects

respon

hypothe

respon

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acute s

termina

correct

system

of the s

of the m

of the s

T

of chal

McEwen a

oss and st

volved in a

ore, we h

onal deficit

There are

avioural as

2005; Cord

selective

we aimed

different a

on.

ND OUTLI

deprivation

al impairm

speculati

of acute

sivity and

esis that s

sivity and

ation. Four

sleep loss

ation (McK

tly, this the

m activation

stress syst

metabolic r

stressfulne

To study e

lenges we

and Seem

tress syste

attentional

hypothesize

s common

only few c

ssessment

dova et al.

and sustai

d to show

attentional

NE OF TH

n is a prob

ents. The

ve. This t

e sleep d

on attenti

sleep depri

d attention

r to six ho

s with sign

Kenna et a

esis aimed

n in concer

tem activa

requiremen

ess nature

effects of s

ere used; n

an, 1999;

em activat

processe

e that stre

nly observe

controlled

and sepa

, 2006). T

ined attent

in a non-

processes

HE THESIS

blem in tod

mechanism

thesis des

deprivation

onal funct

vation, by

nal perform

ours of slee

nificant in

l., 2008).

to reduce

rt with beh

tion in res

nts for ong

of the situa

leep depriv

novelty exp

McEwen,

ion are bo

es (Johnso

ess system

ed after sle

rat studies

rated the

hese two s

tion withou

-confounde

s and the p

S

day’s socie

ms underly

scribes a

n on the

ioning. Th

acting on

mance. Th

ep depriva

creases in

In order to

e stress co

aviour. We

ponse to a

going behav

ation.

vation on s

posure and

1999a; M

oth thought

on et al.,

m activatio

eep depriva

s that asse

different a

studies sh

ut affecting

ed way ho

possible in

ety and is

ying the ad

series of

basal st

e backgro

the stress

his thesis

ation in rat

n sleepine

o interpret

onfounding

e hypothes

a certain s

vioural act

stress resp

d frustrativ

Ge

McEwen, 1

t to affect

1992; Bro

on is also

ation.

essed slee

attentional

owed that

g behaviou

ow acute

nvolvement

associated

dverse effe

studies th

ress resp

ound of the

s systems,

focused

ts has sho

ess for up

the outcom

effects an

size that a

ituation is

tivity, rathe

ponsivity, tw

e non-rew

eneral Intro

999b). Mo

mechanis

own et al.,

o involved

p-deprived

measures

sleep dep

ural control

sleep dep

t of stress

d with men

ects of sle

hat examin

ponse, on

ese studies

may affec

on 4-6 h

own to lea

p to 3 h a

me of our

nd to study

considera

a direct re

er than a re

wo differen

ward stress

oduction

19

oreover,

ms that

2012).

in the

d rats in

(Godoi

privation

. In this

privation

system

ntal and

eep loss

ned the

stress

s is our

ct stress

h sleep

d to an

after its

studies

y stress

ble part

eflection

eflection

nt types

. These

Chapter

20

challen

they h

environ

habitat

be mor

higher

push th

the lab

date. T

perform

time ta

acute s

T

stress

neuroe

proced

experim

were h

as low

per se

activati

(Dobra

proced

radiote

behavio

2004; G

method

Thrivikr

advanc

cages a

room w

I

be mea

r 1

nges were

have a re

nmental ch

(Koolhaas

re relevan

translation

he animals

boratory st

The frustrat

mance, imp

ask (5-CSR

sleep depri

The added

effects

endocrine,

ures. Firs

ments to m

abituated t

as possib

. Habituat

on cause

kovova et

ures can

lemetry an

oural and

Greene et

dology with

raman et

ced sampli

and contac

was not nec

In addition

asured sim

chosen be

elationship

hallenges

s et al., 20

t for huma

nal value to

s towards a

ressors us

tive non-re

pulsivity an

RTT) that

ivation affe

d value an

were min

physiolog

t of all, w

minimize s

to this pro

le to reduc

ion to han

ed by the

al., 1993)

be a serio

nd a small

EEG para

t al., 2007

h catheter

al., 2002;

ing metho

ct with the

cessary.

n, the used

multaneous

ecause the

with the

that the a

006). Stres

an mental

o human s

a stress-ph

sed in exp

eward para

nd motivat

was used

ects differe

nd novelty

nimized w

ical, beha

we applied

stress conf

cess and p

ce stress s

ndling will

e gentle

). In additi

ous confo

implantab

ameters (G

7; Tang et

rized anim

Royo et

ds, the an

animals b

d sampling

sly, freque

y have goo

biology

animal may

sors with g

and psyc

studies (Ko

hysiologica

perimental

adigm also

tion. Toge

d in this th

ent attentio

of the stud

while usi

avioural an

d gentle h

founding e

physical an

system act

reduce th

handling

on, in man

unding fac

ble transmi

Guiol et al

al., 2007)

mals for ta

al., 2004

nimals wer

by the expe

g methods

ently and fo

od ecologi

of the sp

y meet in

good ecolo

hological s

oolhaas et

al ceiling, a

rodent str

allows for

ther with t

hesis, this

nal measu

dies in this

ng optim

nd EEG s

handling s

effects as

nd psycho

tivation by

he extent o

used to

ny rodent

ctor. The

tter to mea

., 1992; V

), and an

king blood

; Abelson

re able to

erimenter o

allow for

or several

cal validity

pecies an

everyday

ogical valid

stress and

al., 2006)

as is the c

ress and s

r behaviou

the 5-choi

allowed u

ures.

s thesis is

mized mea

sampling m

leep depr

much as p

ological stim

y other fact

of HPA ax

keep the

studies, th

studies in

asure seve

Van den, 1

automated

d samples

et al., 20

freely mo

or entering

multiple st

hours, in

y. This mea

nd thus w

life in its

dity are tho

d in additio

. They sho

case with m

sleep rese

ral assess

ce serial r

us to asse

that confo

asurement

methodolo

rivation in

possible. A

mulation w

tors as sle

xis and ad

animals

he used sa

this thes

eral physio

1994; Leon

d blood sa

s (Steffens

005). Usin

ove in thei

g the exper

tress read-

the same

ans that

with the

natural

ought to

on have

ould not

many of

earch to

ment of

reaction

ess how

ounding

ts with

ogy and

all our

Animals

was kept

eep loss

drenalin

awake

ampling

is used

ological,

n et al.,

ampling

s, 1969;

ng such

ir home

rimental

-outs to

e freely-

moving

various

confou

studies

respon

activati

provide

and fre

recove

recove

T

EEG re

concert

correla

strengt

depriva

I

behavio

corticos

investig

method

addres

respon

confron

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novelty

presum

course

the beh

of the

reflectio

of the s

g subject.

s relevant

nding stre

s combing

se has be

on, but als

e an as co

equent as

ry. This is

ry time (Ko

The parall

ead-outs in

t with beh

te with the

then the i

ation and o

In chapte

oural, phys

sterone) a

gated whe

ds. Second

s this, th

ses were

ntation with

er, this int

xamined w

y exposure

med cognit

of the nov

havioural r

hormonal

on of the m

stressful na

Many exp

stress pa

ss effects

sleep dep

een measu

so the EE

omplete as

ssessment

important

oolhaas et

el measur

n this thes

aviour to f

e stress sy

interpretati

our concep

er 2 we a

siological (

and EEG

ether stres

dly, this st

he behavi

studied b

h a novel c

erpretation

whether th

e can be e

tive state o

velty-induc

responses

and phys

metabolic r

ature.

perimental

rameters

have ofte

privation w

ured. In th

G and beh

s possible

t of these

since each

al., 1997).

rements of

is also allo

further stu

ystem activ

ion and c

pt of stress.

aimed to v

(blood pres

response

ss confoun

tudy aimed

ioural, ph

before, du

cage is co

n is simply

he neuroe

explained

of aversion

ced physio

were used

siological r

requiremen

rodent stu

in parallel

en hamper

ith the stre

is thesis,

havioural a

picture. A

e measure

h activated

.

f physiolog

owed analy

dy whethe

vation. The

characteris

.

validate th

ssure, hea

es during

nding effec

d to furthe

ysiological

uring and

nsidered a

y based on

endocrine

by increas

n. To stud

ological and

d. This app

responses

nts for the

udies lack

and if the

red the int

ess respon

both the S

activity res

Another ad

ements to

d process h

gical, neur

ysis of the

er the cha

ese correl

sation of t

he samplin

art rate, bo

undisturbe

cts were r

er evaluate

l, plasma

after nov

a psycholo

the occur

and phys

sed behav

dy this, de

d hormona

proach allo

to novel

normal ong

Ge

the poss

ey do hav

terpretation

nse, only t

SAM syste

sponses w

dded-value

o see the

has its own

roendocrine

e stress sy

nges in be

ational ana

the conse

ng method

dy temper

ed contro

reduced w

e the conc

corticoste

vel cage e

ogical and

rrence of a

siological

ioural activ

etailed ana

al response

owed for fu

cage expo

going beha

eneral Intro

ibility to m

ve this pos

n. In most

the cortico

em and HP

were measu

e is the lo

ir dynami

n time cou

e, behavio

stem activ

ehavioural

alyses will

equence o

ds by me

rature and

l condition

with our sa

cept of stre

erone and

exposure.

aversive s

a stress res

activation

vity rather

alyses of t

es in conc

urther clar

osure as a

avioural ac

oduction

21

measure

ssibility,

t rodent

osterone

PA axis

ured, to

ng-term

cs and

rse and

oural en

vation in

activity

l further

of sleep

easuring

plasma

ns. We

ampling

ess. To

d EEG

Forced

stressor.

sponse.

during

r than a

he time

cert with

rification

a direct

ctivity or

Chapter

22

C

affects

confou

method

depriva

determ

hormon

during

of resp

depriva

I

investig

novelty

sleep d

a brief

locomo

corticos

were ex

this cha

by stud

of sleep

C

stressfu

and sh

everyda

conditio

Next, w

of the

control

stress s

we use

investig

press

r 1

Chapter 3

the basa

nding effe

ds as in c

ation were

ine the r

nal stress

sleep depr

ponses. T

ation shoul

In chapter

gate how 4

y exposure

deprived fo

recovery

otor activit

sterone as

xamined fr

apter the g

dying the s

p deprivati

Chapter 5

ul conditio

hould invo

ay life in

oning task

when lever

expected

. Such los

systems an

ed the sam

gated how

behaviour

3 aimed to

al activity

ects of the

chapter 2,

e reduced.

relationship

parameter

rivation bu

his study

d be interp

r 4 the find

4 and 6 h o

e and how

or 4 or 6 h

of the slee

ty, heart

s well as s

rom before

gentle han

sleep-wake

on.

5 continued

on needs t

olve an en

its natura

k in which

pressing i

behaviou

ss of cont

nd has bee

me samplin

w the stress

is affecte

assess h

of the s

e sampling

also pos

Detailed

p between

rs. These p

t also after

also exa

preted as s

dings and

of acute sl

w stress ph

using the

ep depriva

rate, bloo

sleep-wake

e sleep dep

ndling sleep

e distributio

d on the fi

to contain

nvironment

al habitat.

rats are t

s suddenly

ural conse

trol has be

en describ

ng and slee

s response

ed by 6

ow acute

stress sys

g procedur

ssible stre

time and

n changes

parameters

r sleep dep

mined wh

stressful.

methods o

leep depriv

hysiology

gentle han

ation period

od pressu

e distributio

privation un

p deprivati

on and NR

ndings of

uncontrol

tal challen

Therefore

trained to

y no longe

equence a

een assoc

ed as frust

ep depriva

e to rewar

h of slee

4-h gentle

stems. Be

res by usi

ss confou

correlatio

s in beha

s were not

privation in

hether 4 h

of chapter

vation affe

is involved

ndling slee

d, rats we

ure, body

on and NR

ntil recove

ion method

REM delta

chapter 4.

llability an

nge which

e chapter

lever pres

er rewarded

and suppo

ciated with

trative non

tion metho

rded and n

p depriva

e handling

sides red

ing the sa

unding effe

onal analys

avioural, p

t only mea

n order to s

h of gentle

r 2 and 3 w

ect the stre

d. To stud

ep deprivat

re expose

temperat

REM delta

ry from no

d was also

power du

. It is sugg

d unpredi

h the anim

5 focused

ss for food

d, the anim

osedly exp

h a strong

n-reward st

ods as in c

non-reward

tion. We

sleep dep

ucing the

ame exper

ects of the

sis were u

physiologic

asured befo

study the re

e handling

were comb

ess respon

dy this, rat

tion metho

ed to nove

ture and

power res

velty expo

o further va

ring and a

gested that

ctability el

mal may m

d on an o

d reinforce

mal faces a

periences

activation

tress. In ch

chapter 4 b

ded opera

also stud

privation

stress

rimental

e sleep

used to

cal and

ore and

ecovery

g sleep

bined to

sivity to

ts were

od. After

lty. The

plasma

sponses

osure. In

alidated

after 6 h

t a truly

lements

meet in

operant-

ements.

absence

loss of

n of the

hapter 5

but now

nt lever

ied the

respon

stress

respon

recove

depriva

the ope

C

detail o

samplin

animals

a light

The 5

attentio

Beside

temper

the use

I

ses to frus

system ac

ses were

ry from th

ation affect

erant task.

Chapter 6

on attention

ng and sle

s were ass

stimulus p

-CSRTT a

on, such a

s assess

rature and

ed procedu

In chapter

strative no

ctivation w

not only a

is task. An

ts the perfo

6 continued

nal function

eep depriva

sessed in t

presented r

allows clo

as selectiv

ing these

polysomn

ures.

r 7 the res

n-reward i

was related

nalysed du

nother aim

ormance,

d on the fi

ning after 6

ation meth

the 5-CSR

randomly i

ose obser

ve attention

e attention

nographic

sults of the

n concert

d to behav

uring opera

m of this st

motivation

ndings of c

6-h gentle

hods were

RTT. In the

in one of 5

rvation of

n, sustaine

nal aspec

parameter

e experim

with behav

vioural act

ant task ex

tudy was

and impu

chapter 4

handling s

used as i

5-CSRTT

5 holes in

different

ed attentio

cts, gross

rs were al

ents are s

Ge

viour to as

tivity. To e

xposure b

to assess

ulsivity of th

and 5 and

sleep depr

in chapter

, rats dete

order to g

compone

on and be

locomoto

so measu

summarize

eneral Intro

ssess whet

examine t

ut also du

how acut

he animals

d focused

ivation. Th

4 and 5 b

ct and res

get a food

ent proces

ehavioural

or activity

red to con

ed and disc

oduction

23

ther the

his, the

ring the

te sleep

s during

in more

he same

but now

pond to

reward.

sses of

control.

y, body

ntrol for

cussed.

Chapter 2

Physiological and hormonal responses to novelty exposure in rats are mainly related to ongoing

behavioural activity

W. Beerling1, 2, J.M. Koolhaas2, A. Ahnaou1, J.A. Bouwknecht1, S.F. de Boer2,

P. Meerlo2 and W.H.I.M. Drinkenburg1

1 Department of Neuroscience, Janssen Research & Development, a division of

Janssen Pharmaceutica N.V., Turnhoutseweg 30, 2340 Beerse, Belgium; 2 Department of Behavioural Physiology, University of Groningen, Nijenborgh 7, 9747 AG

Groningen, The Netherlands

Physiology & Behavior 2011, 103:412-20

Chapter

26

ABSTR

Stress

stress r

of cogn

may h

adrenom

only act

body fo

a certai

behavio

clarify

respons

confron

stressor

respons

induced

rats, w

implanta

samplin

for furth

induced

corticos

The late

but all

(locomo

correlat

observa

present

closely

interpre

appropr

emphas

hormon

r 2

RACT

research ha

response is

itive experie

ave malad

medullary (

tivated in re

r behaviour

n situation c

oural activity

this, beha

ses to nove

tation with

r. However

se. The pre

d responses

which allow

able transm

ng system w

her behavi

d significant

sterone toge

ency to rea

had recove

otor activity

ted with tha

ations show

t results ind

related to t

etation in t

riate than

sizes the ad

al paramete

as been do

bad. Cons

ence of ave

daptive an

SAM) syste

esponse of

r. Therefore

can be a di

y, rather tha

avioural, ph

el cage expo

a novel c

r, this inte

esent study

s. Different

wed correla

mitter com

were used.

oural obse

t increases

ether with a

ach significa

ered within

y and EEG

at of heart

wed mainly

dicate that t

he ongoing

erms of m

the frequ

dded value

ers under c

ominated by

sequently, th

ersiveness

nd patholog

em and the

the organi

e, a conside

rect reflecti

an a reflecti

hysiological

osure were

cage has b

erpretation

aimed at d

t parameter

ational com

bined with

A camera

ervational a

in locomo

a complete

ance and th

30 min af

G wakefuln

rate, blood

explorative

the novelty-

g, mainly ex

metabolic s

ently used

of simultan

controlled, n

y a circular

he stimulus

involving un

gical cons

e hypothala

sm to chall

erable part o

on of the m

ion of the a

l, hormona

studied in

been interp

is simply

detailed an

rs were me

mparisons.

h permanen

was positio

analysis. Th

otor activity,

lack of sle

he duration

fter termina

ness durati

d pressure

e behaviou

-induced ph

xplorative be

upport of

d stress in

neous asse

non-confoun

r type of re

s is often in

ncontrollabi

sequences.

amic-pituitar

enges, but

of the classi

metabolic req

versive nat

al and ele

adult male

preted as a

based on

nalysis of th

easured sim

Hereto, ra

nt catheter

oned above

he results

, heart rate

eep as com

n of respons

ation of nov

on) respon

and plasm

r in respon

hysiological

ehavioural a

ongoing be

nterpretatio

ssment of b

nding condit

easoning th

terpreted a

ility and unp

However,

ry-adrenal (

also prepa

ical stress s

quirements

ure of the s

ectroenceph

Sprague-D

a psycholo

the occur

he time cou

multaneous

adiotelemet

rs and an

e the cage t

show that

e, blood pre

mpared to th

ses varied

velty. The b

nse pattern

ma corticost

nse to nove

and hormo

activity indu

ehaviour s

on. The pr

behavioura

tions.

hat occurren

s stressful

predictabilit

the sym

(HPA) axis

are and sup

system activ

for normal

situation. In

halographic

Dawley rats

gical and

rrence of a

urse of the

ly in freely

try using

automate

to make rec

t novelty e

essure and

he control s

across par

behavioura

n was sign

erone. Beh

elty. Theref

onal respon

uced by nov

eems to b

resent stu

l, physiolog

nce of a

in terms

ty, which

mpathico-

are not

pport the

vation to

ongoing

order to

c (EEG)

. Forced

aversive

a stress

novelty-

moving

a small

d blood

cordings

exposure

plasma

situation.

rameters

l activity

nificantly

havioural

fore, the

nses are

velty. An

be more

dy also

gical and

INTRO

Organis

which

adreno

the two

such c

(adrena

bloodst

adapt

Reisine

activate

problem

hormon

cognitiv

which m

has ho

though

authors

De Klo

reason

often in

HPA a

system

of bloo

suppor

Leal-Ce

activati

normal

the situ

activati

to ave

reward

ODUCTION

sms are c

they have

omedullary

o most imp

hallenges.

alin and no

tream, whi

adequatel

e, 1984; J

es these s

m in stress

nal activati

ve experie

may have

owever not

this adap

s (Selye, 1

oet et al.,

ing that oc

nterpreted

axis activa

m and HPA

od to activ

rt the body

erro et al.,

on to a ce

ongoing b

uation (Ko

on of the c

rsive, unc

ing, contro

N

constantly

e to resp

(SAM) sy

portant ne

Activation

oradrenalin

ich have a

y to the

Johnson e

so-called s

s research

ion of the

ence of ave

maladapti

t only a m

ptive nature

950; Selye

2005), s

ccurrence o

as stressf

tion may

axis also

ve organs

y for beha

2003). Th

ertain situa

behavioura

oolhaas et

classical ne

controllable

ollable situ

subjected

pond adeq

ystem and

uroendocr

n of these

n) and glu

a variety o

demandin

t al., 1992

stress sys

h. Stress is

two main

ersiveness

ive and pa

maladaptive

e of the st

e, 1976; M

tress rese

of a stress

ful in term

not be a

have a ma

and tissu

aviour (Axe

herefore, a

tion is a di

al activity, r

al., 2011)

euroendoc

e situation

ations like

to deman

quately in

hypothala

rine pathw

pathways

ucocorticoid

f effects th

ng internal

2). A stim

stems. How

s not only

stress sys

s, involving

athological

e nature, b

tress respo

McEwen an

earch is s

s response

ms of avers

sufficient

ain role in e

ues, and a

elrod and

considera

irect reflec

rather than

). In agree

crine stress

ns but som

e sexual be

Novelty ex

nding inter

order to

amic-pituita

ays that a

results in

ds (cortico

hat enable

l and exte

mulus is co

wever, the

y interprete

stems. It is

g uncontro

conseque

but has al

onse has

nd Wingfie

still domina

e is bad. Co

siveness. H

indicator

energy hom

are therefo

Reisine, 1

able part of

ction of the

n a reflecti

ement with

s systems

metimes a

ehaviour, w

xposure and

rnal and e

survive.

ary-adrena

are activate

n release o

osterone or

e organism

ernal stim

onsidered

ere is a se

ed as the

s also often

llability an

ences. The

lso adaptiv

been emp

ld, 2003; K

ated by a

onsequent

However,

for such s

meostasis

ore known

984; John

f the classi

e metabolic

on of the a

h this, stud

not only o

also in re

winning a

d the stress

external st

The symp

al (HPA) a

ed in resp

of catecho

r cortisol)

ms to respo

muli (Axelro

stressful w

erious con

physiologi

n interprete

d unpredic

e stress re

ve aspects

phasized b

Korte et al

a circular

tly, the stim

SAM syste

stress. Th

and redist

n to prepa

nson et al.

ical stress

c requirem

aversive na

dies show

ccurs in re

sponse to

social inte

response

27

timuli to

pathico-

axis are

onse to

lamines

into the

ond and

od and

when it

nceptual

cal and

ed as a

ctability,

esponse

s. Even

y many

., 2005;

type of

mulus is

em and

he SAM

tribution

are and

., 1992;

system

ents for

ature of

wed that

esponse

o highly

eraction,

Chapter

28

and foo

al., 198

et al., 2

terms

conside

respon

In our

behavio

and ph

truly st

the be

occur (

reflecte

Boer e

Koolha

I

respon

stress

stresso

al., 200

than w

novel a

forced

and Fr

system

exposu

al., 197

1983; A

al., 198

al., 20

observa

an ave

Howev

r 2

od/water in

84; De Boe

2012).Henn

of a psyc

ered as a

ses are a

view, whe

oural activ

ysiology s

tressful in

ehavioural

(Koolhaas

ed in the re

et al., 199

aas et al., 2

In order to

ses to nov

research

or because

08). Also,

hen the an

area (Miss

exposure

riedman,

ms in resp

ure, and us

73; Pfister

Armario et

89; De Boe

005; De G

ation of th

ersive stre

er, becaus

ntake (Sch

er et al., 19

nessy and

hoendocrin

a compone

reflection o

en activatio

vity induce

hould occu

terms of u

activity le

et al., 20

ecovery of

90a; Garcia

2011).

o clarify this

velty expo

in rodents

e it is an u

forced exp

nimal is giv

slin et al.,

to a novel

1968). Ma

ponse to

sing it as a

and King

t al., 1986;

er et al., 1

Groote and

is literature

essor is s

se laborato

uurman, 1

990a; Arnh

Levine dis

ne hypoth

ent of a u

of changes

on of the s

d by the s

ur (Koolhaa

uncontrolla

evels and

11). Analy

responses

a et al., 2

s, we stud

osure, a st

s. The imp

unknown a

posure to a

ven the op

1982). In

cage resu

any studie

novelty, a

an acute,

, 1976; He

; Flaherty e

1990b; Buw

d Linthors

e shows th

imply bas

ory rats ex

980; Brons

hold et al.,

scussed th

esis; they

unified sys

s in arousa

stress syst

situation, c

as et al., 2

able and u

the phys

ysis of the

s rather tha

2000; Fish

ied the be

timulus tha

plicit theor

and potenti

an unfami

pportunity t

n 1968, Ad

ults in a ra

es followe

and more

aversive a

ennessy et

et al., 198

walda et a

st, 2007;

hat the inte

sed on the

xperience s

son and D

2009; Koo

hese conce

y suggest

stem of a

al level (He

tems is ma

clear assoc

2011). For

unpredictab

iological/ho

literature

an the initia

h et al., 2

havioural,

at has a lo

ry is that

ially dange

liar area is

to freely m

del and Fr

pid rise of

d, showin

specifical

and psycho

t al., 1979

6; Muir an

al., 1993; M

Whyte an

erpretation

e occurren

such a no

esjardins,

olhaas et a

epts of stre

that the H

arousal an

ennessy a

ainly relate

ciations be

a situation

ble, a diss

ormonal r

suggests

ation (Schu

2005; Arnh

physiologi

ong history

this may

erous situa

s consider

move betwe

riedman re

corticoste

ng activatio

lly for rat

ological str

9; Pfister, 1

nd Pfister,

Meerlo et a

nd Johnso

n of novel c

nce of a

vel cage c

1982; Shir

al., 2011; B

ess and aro

HPA axis

d that HP

and Levine

ed to the o

etween be

n to be con

sociation b

responses

that this

uurman, 19

hold et al.

ical and ho

y in exper

represent

ation (Gag

red more s

een a fami

eported th

rone in rat

on of the

s to nove

ressor (Ba

1979; Bret

1986; De

al., 1999; T

on, 2007).

cage expo

stress res

challenge o

raishi et

Buwalda

ousal in

can be

PA axis

, 1979).

ongoing

ehaviour

nsidered

between

should

may be

980; De

, 2009;

ormonal

rimental

a mild

liano et

stressful

liar and

hat brief

ts (Ader

e stress

el cage

assett et

tt et al.,

Boer et

Tang et

. Close

osure as

sponse.

once or

twice a

taken p

already

stress p

1972).

cognitiv

T

hormon

15-min

of the

levels t

the ph

importa

control

proced

implant

1992; V

2007),

perman

2002; R

above

The fo

pressu

EEG re

behavio

informa

this stu

respon

whethe

a week as p

place (Ste

y showed i

pathology

Therefore

ve state of

The prese

nal and ele

novel cag

novelty-ind

together w

ysiologica

ant to no

led cond

ures. This

table trans

Van den B

combined

nently cath

Royo et al.

the cage

ollowing pa

re, body t

ecordings w

oural obse

ation about

udy was to

ses are re

er the frequ

part of the

ein, 1966;

in 1972, it

but the de

e, exposur

f aversion a

ent study a

ectroencep

ge exposur

duced res

with behav

l and hor

otice that

itions wit

s was achi

smitter to m

Buuse, 19

d with a

heterized, f

., 2004; Ab

to make r

arameters

temperatur

were addit

ervations a

t the ongoi

determine

elated to t

uently used

regular cle

Groves an

is not the

gree in wh

re to novel

and unpred

aimed at fr

phalograph

re in rats. T

ponses. S

vioural obs

monal res

measurem

h minimiz

ieved and

measure p

94; Leon

an automa

freely-mov

belson et a

recordings

were me

re, EEG a

tionally ana

and locomo

ing behavi

e whether

the ongoin

d stress int

eaning reg

nd Thomp

e physiolog

hich it can

ty may be

dictability.

requent re

hic (EEG)

This allowe

Simultaneo

servations

sponse pa

ments we

zed confo

controlled

physiologic

et al., 200

ated bloo

ving anima

al., 2005).F

for furthe

easured: l

and plasm

alysed for

otor activit

oural activ

the novelty

ng behavio

terpretation

Novelty ex

gime, habit

son, 1970

gical nature

be predicte

only minim

cording of

parameter

ed detailed

us registra

allowed c

atterns wit

ere taken

ounding f

d for by ra

cal and EE

04; Greene

od sampli

ls(Steffens

Furthermor

er behaviou

ocomotor

a corticos

vigilance s

ty measure

vity of the a

y-induced

oural activ

n is correc

xposure and

tuation pro

0; Thomps

e of a stim

ed and/or c

mally stres

f behaviou

rs over tim

d analysis o

ation of be

orrelationa

h ongoing

while m

factors d

adioteleme

EG parame

e et al., 2

ng system

s, 1969; Th

re, a came

ural obser

activity, h

terone con

states and

ements the

animals. Th

physiologi

vity induce

t.

d the stress

ocesses ma

on, 2009)

mulus that

controlled

ssful in ter

ral, physio

me in resp

of the time

ehavioural

al compari

g behaviou

aintaining

ue to sa

etry using

eters (Guio

2007; Tang

m connec

hrivikrama

ra was pos

rvational a

heart rate

ncentration

together w

ese gave d

he primary

ical and ho

d by nove

response

29

ay have

. Weiss

induces

(Weiss,

ms of a

ological,

onse to

e course

activity

sons of

ur. It is

strictly

ampling

a small

ol et al.,

g et al.,

cted to

n et al.,

sitioned

analysis.

, blood

ns. The

with the

detailed

y goal of

ormonal

elty and

Chapter

30

METHO

Anima

In a se

rats (H

were u

polycar

Immed

experim

Interna

(AccuS

above

1°C), c

30-min

for weig

experim

Surger

Surgery

mainte

weight)

record

cortical

intrape

et al.,

measu

measu

subcuta

through

to the

screws

0.84, D

r 2

ODS

ls and hou

eries of 2 e

Harlan, Hor

sed. For a

rbonate ca

iately afte

mental set-

ational, St

Sampler M

the cage.

controlled h

rise and d

ghing purp

mental prot

ry

y was pe

nance). Th

) was adm

gross loco

l EEG (T

ritoneally a

2007). Th

re blood

rements, a

aneously t

h holes in

midline an

s and denta

DiLab) ena

using

experiment

rst, The N

at least 2 w

ages (43x

er surgery,

-up. This s

. Paul, M

icro, DiLab

The rats

humidity (5

dim period

poses and

tocols were

rformed u

he analges

ministered

omotor ac

TL11M2-C

and attach

e catheter

pressure.

animals we

to the skul

the skull. T

nd 6 mm p

al cement

abling blo

ts, two bat

Netherlands

weeks prior

x27x39 cm

each an

set-up cons

MN, USA)

b, Lund, Sw

were hous

50 ± 10%)

with lights

standard r

e approved

nder O2-N

sic Piritram

subcutane

ctivity, hea

C50-PXT,

hed to the

r of the tra

To place

ere placed

l and the b

These elec

posterior to

. In additio

od sample

tches with

s), weighin

r to surgery

m) contain

imal was

sisted of a

and an

weden). F

sed in a ro

and a fixe

s on at 06

rat chow a

d by the lo

N2O-isoflur

mide (dipid

eously at t

art rate, blo

DataScien

abdomina

ansmitter w

e the two

in a stere

bare ends

ctrodes we

o bregma

on, a heart

es to be

in total 9 a

ng 310-330

y, animals

ning bedd

placed w

a radiotelem

automate

urthermore

oom with c

ed 12 : 12

.00h. The

nd water w

cal ethical

rane anae

olor, 0.025

the start o

ood press

nces Inte

al wall to e

was insert

biopotent

eotaxic app

were plac

ere placed

and were

t catheter

collected

adult male

0 g at the

were indiv

ing and c

ithin its ho

metry set-u

d blood

e, a camer

constant te

h light/da

animals w

were provid

committee

sthesia (5

5 mg/kg, 0

of surgery

ure, body

ernational)

ensure stab

ted in the

tial leads

paratus. Th

ced in con

3 mm on

anchored

(polyureth

in freely

e Sprague-

e time of s

vidually ho

cage enric

ome cage

up (DataS

sampling

ra was pos

emperatur

rk regime

were daily h

ded ad libi

e.

5% inducti

0.1 ml/100

. A transm

temperatu

was im

bilization (

femoral a

for cortica

he leads w

tact with th

either side

d to the sk

ane; ID: 0

moving ra

-Dawley

surgery,

oused in

chment.

e in the

ciences

system

sitioned

re (21 ±

using a

handled

itum. All

on; 2%

g body

mitter to

ure and

mplanted

(Greene

artery to

al EEG

were led

he dura

e lateral

kull with

0.6, OD:

ats was

implant

through

The oth

the skin

spiral to

samplin

infusion

ensure

weeks

Experi

Two ex

and us

differen

taken t

novelty

days in

design,

paralle

parame

was sa

further

not be

blocked

presen

novelty

All exp

(i.e. the

experim

connec

and blo

ted (Steffe

h the right

her end wa

n in the do

o a swivel

ng machin

n pump giv

the cathe

before sta

mental de

xperiments

sing the e

nce betwe

together. A

y-exposed

n between

, all anima

l to reduce

eters were

ampled aut

behaviour

analysed

d blood sa

t in both

y-exposed

perimental

e resting p

mental day

cting them

ood sampl

ens, 1969;

jugular ve

as led subc

orsal region

and conn

ne. After s

ving a con

ter to stay

rt of the ex

esign

s, with two

exact same

en the two

After recov

conditions

sessions

als were e

e variability

e measure

tomatically

ral observa

further du

ampling ca

groups re

condition o

procedure

phase) and

y started w

to the aut

ing started

; Thrivikra

ein with the

cutaneous

n of the ne

nected eith

surgery, th

ntinuous inf

y open. The

xperiments

batches o

e procedu

o experim

very from s

s using a ba

and using

exposed to

y among a

ed continu

y and repe

ational ana

ue to insuf

atheters. A

sulting in

of which d

es were pe

d potentiall

with weighin

tomated b

d simultane

man et al

e end reac

sly through

eck. The ca

er to the in

he animals

fusion (sal

e animals

s.

of animals,

ures. Statis

ents and

surgery, ra

alanced an

g a standa

o both con

animals and

ously and

eatedly. Fu

alysis. The

fficient qua

As a result

n=7 for th

ata of four

erformed d

ly disturbin

ng the ani

lood samp

eously at l

Novelty ex

l., 2002).

ching the e

a Dacron

atheter wa

nfusion pu

s were im

line + hepa

were allow

, were don

stical anal

therefore

ats were su

nd cross-ov

ard circadia

nditions. S

d behaviou

automatic

urthermore

e data of a

ality of the

t, the sam

he control

r animals i

during the

ng stimuli w

mals, activ

pling mach

least 1 h l

xposure and

The cathe

entrance o

button tha

as then con

ump or the

mediately

arin: 10 IU

wed to reco

ne with 4 w

ysis show

the data o

ubjected to

ver William

an time w

even set-u

ural, physi

cally. Con

, recording

a number

eir telemet

e animals

condition

s presente

first half o

were caref

vating their

hines. Tele

ater with a

d the stress

eter was i

of the right

at was atta

nnected th

automate

connected

U/ml; 0.24

over for at

weeks in b

wed no sig

of all grou

o either co

ms design w

indow. Us

ups were

ological an

ncomitantly

gs were m

of subject

try signals

were not

and n=6

ed in both

of the light

fully avoide

r transmitt

emetric rec

a 30-min b

response

31

nserted

atrium.

ached to

rough a

d blood

d to an

ml/h) to

t least 2

between

gnificant

ups was

ontrol or

with 3-5

sing this

used in

nd EEG

y, blood

made for

ts could

s and/or

always

for the

groups.

t phase

ed. The

ers and

cordings

baseline

Chapter

32

period,

h post-

Novelt

Exposu

and co

min to

clean, e

enterin

collecti

control

experim

Biotele

Gross

EEG

(DataS

and EE

obtaine

Becaus

animal

were re

by a co

from b

and bo

bins. E

(Medca

at 40 H

EEG p

states.

of high

r 2

followed b

novelty pe

y exposur

ure to nove

-workers (

gently pick

empty cag

g the expe

ng the t =

conditions

mental room

emetric da

locomotor

were mo

Sciences In

EG depend

ed by coun

se the tra

were hard

eceived by

omputer us

lood press

ody tempe

EEG bio-po

areFlaga, R

Hz. The vig

power spec

Non-Rapid

amplitude

by a 15-mi

eriod.

re

elty was p

De Boer e

k up the ra

e compara

erimental ro

15 min blo

s, animals

m.

ata acquis

activity, h

onitored

nternationa

dent freque

nting the n

nsmitter w

dly detecte

y an antenn

sing Dataq

sure meas

rature data

otential rec

Reykjavik,

gilance sta

ctrum for

d Eye Mov

e EEG wav

in novelty e

performed a

et al., 1990

at from its

able to its h

oom, brief

ood sample

s were left

sition and

heart rate,

telemetrica

al). The tra

ency modu

number of

was implan

d by the re

na board p

quest Labp

surements.

a was sam

cordings w

Iceland) w

ates were

each epoc

vement (N

ves and pr

exposure o

according

0b). The ex

home cag

home cage

handling a

e, rats were

t undisturb

analysis

blood pre

ally using

ansmitter

ulated sign

f changes

nted in th

eceiver, bu

placed und

pro softwa

Locomoto

mpled in 1

were impor

with a lowe

determine

ch was us

REM) slee

redominant

or control p

to the pro

xperimente

ge at t = -1

e. Novelty e

and forced

e returned

bed in thei

essure, bod

g the D

emitted te

nals. For lo

in signal

e abdome

ut horizonta

der each an

re. Heart r

or activity,

0-s epoch

rted into S

er cut off at

d off-line i

sed to aid

ep was sco

t EEG pow

period with

otocol desc

er entered

1 min and

exposure t

d novel cag

to their ho

r home ca

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strength o

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hs and ave

Somnologic

t 0.7 Hz an

n 4-s epoc

d in discrim

ored based

wer in the d

h subseque

cribed by d

the room a

place it in

therefore in

ge exposur

ome cages

ages in the

ature and

A.R.T.

e, blood p

activity, da

of the tran

l changes

s were. All

ge and pro

s were ca

e, blood p

eraged into

ca 3.2.0 s

nd a highe

chs. A con

minating b

d on the pr

delta range

ent a 2-

de Boer

at t = -2

a new,

ncluded

re. After

s. Under

e same

cortical

System

pressure

ata was

nsmitter.

s of the

signals

ocessed

lculated

pressure

o 5-min

software

r cut off

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between

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e (0.5-4

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charact

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EEG w

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samplin

minimiz

min an

rpm. S

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immuno

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5.0 (No

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period

control

behavio

drinking

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not affe

therefo

nd lack o

terized by

Hz) with re

onal twitch

with a lack

t of time s

blocks.

sampling

was sampl

ng machin

ze possible

d were sto

ubsequent

analysed

oassay (M

with a sens

iour

our was s

oldus, Wag

ne period (

iately after

starting im

animals,

oural clas

g); 3) gro

ours (e.g.

ected by

ore not inc

of body

highly reg

educed low

hes. Wakef

k of visible

pent in wa

and assa

ed using th

ne. Animal

e stress-co

ored inside

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for cortico

Mouse/Rat

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cored blin

geningen,

t = -25 unt

r the anima

mmediately

the sam

sses were

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dig/move b

novelty ex

cluded in

movement

ular low am

wer freque

fulness wa

e theta do

akefulness,

ays

he jugular

s were ha

onfounding

e the mach

of plasma

osterone,

Corticoste

.0 ng/ml.

dly and of

The Neth

til t = -5 m

al was plac

y after the

me circadia

e defined:

ncluding s

bedding, s

xposure an

the graph

t. Rapid

mplitude E

ncies and

as scored b

ominance,

, NREM sle

vein cathe

abituated t

g effects of

hine at 4 °

was store

in duplica

erone125I R

ff line by o

erlands). T

min), the 15

ced in the n

animal wa

an time p

1) immo

scratching

stretch and

nd was pr

hs. The r

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general la

based on i

and frequ

eep and R

eter connec

to the bloo

f it. 30-µl s

°C until ce

ed at –80

ate, using

RIA Kit, M

one experim

Three peri

5-min nove

novel cage

as returned

periods we

obility; 2)

); 4) rear

yawn). Th

resent in a

relative du

xposure and

vement (R

a dominanc

ack of body

irregular lo

uent body

REM sleep

cted to the

od sampli

samples w

entrifuged f

°C until a

a double

P Biomed

menter us

ods were

elty exposu

e, and a 20

d to its ho

ere score

consump

ring; 5) s

he 6th beha

a low perc

uration (tim

d the stress

REM) slee

ce of theta

y moveme

ow-amplitu

movemen

was calcu

e automate

ng proced

ere taken

for 5 min a

assayed. S

e antibody

icals, Solo

ing The O

scored; a

ure period

0-min post-

me cage.

d. The fo

ption (eatin

sniffing; 6

avioural cla

centage a

me spent

response

33

ep was

activity

nts with

de, fast

nts. The

ulated in

ed blood

dures to

every 5

at 3210

Samples

y radio

on, OH,

Observer

20-min

starting

-novelty

For the

ollowing

ng and

) other

ass was

nd was

on the

Chapter

34

behavio

behavio

Statist

To ass

respon

epsilon

Treatm

levels)

cross-o

presen

rather

perform

conditio

the bas

into the

calcula

recordi

(TMAX)

calcula

duratio

togethe

ANOVA

novelty

paired

parame

reache

correla

respon

and EE

betwee

other r

r 2

our expres

oural class

ics

ess the eff

ses, a re

n (ε) for v

ment (novel

and the di

over design

t in both g

than as

med to dete

ons differe

seline, nov

e dynamic

ations were

ng period

were det

ated acros

n a reduct

er with the

A with trea

y exposure

t-test was

eters were

d their VM

tion coeffic

se pattern

EG wakef

en the loco

responses,

ssed as pe

ses for the

fect of nov

epeated m

violation o

lty exposu

fferent tim

n was initi

groups. Th

within-sub

ermine the

ed. Paired

velty expos

s of the te

e performe

and the

ermined f

s these v

tion occurre

time point

atment as

on VMAX /

s used to

e significan

MAX / VMIN

cient test w

s over tim

fulness du

omotor act

, as this w

ercentage

three perio

velty on the

measures

of the hom

re vs. con

e points or

ially used,

herefore, t

bject facto

e specific ti

t-tests we

sure and po

elemetric a

ed. The ma

time point

for each i

values for

ed and the

t at which

within-sub

VMIN and T

assess w

ntly differe

around th

was used t

e between

uration res

tivity, EEG

will show

of the ob

ods.

e behaviou

ANOVA w

mogeneity

ntrol) was u

r periods a

the data

reatment w

or. When

ime points

ere used t

ost-novelty

and cortico

aximum va

t at which

ndividual

each para

erefore the

this minim

bject varia

TMAX / TMIN

whether the

ent in orde

he same t

to compute

n the locom

sponses. T

wakefulne

to what e

servation t

ural, physio

with Gree

in varian

used as be

as within-su

of the sam

was used

appropria

at which n

o determin

y exposure

osterone m

alue (VMAX

h this max

separately

ameter. F

e minimum

mum was a

ble was u

N. For the n

e TMAX / T

er to see

time point

e correlatio

motor activ

The main

ess duratio

extent beh

time) was

ological, ho

enhouse-G

nce assum

etween-su

ubject facto

me animals

as betwee

ate, post-h

novelty-exp

ne the diff

e period. To

measureme

X) reached

ximum valu

y and a g

or NREM

value (VM

achieved (T

sed to ass

novelty-exp

TMIN value

whether t

s. The Pe

ons for the

vity, physio

focus was

on respons

havioural a

calculated

ormonal an

Geisser co

mption was

ubjects fact

or. Even th

s was not

en-subjects

hoc t-test

posed and

ferences b

o get more

ents, the fo

during the

ue was ac

group mea

and REM

IN) was ca

TMIN). An o

sess the e

posed cond

s of the d

these para

earson’s B

e novelty-e

ological, ho

s on corre

se pattern

activity lev

d for all

nd EEG

orrection

s used.

tor (two

hough a

always

s factor

s were

d control

between

e insight

ollowing

e whole

chieved

an was

M sleep

lculated

one-way

effect of

dition, a

different

ameters

Bivariate

exposed

ormonal

elations

and all

vels are

reflecte

mean v

was se

Only v

measu

on the

comput

softwar

values

SEM.

RESUL

Dynam

exposu

Locomo

ANOVA

interact

p<0.00

activity

1 pane

(t=2.5

(t=17.5

The se

control

control

over th

indicati

ed in the p

value for e

et together

values of

rement we

paramete

te a corre

re (SPSS i

<0.05 and

LTS

mics of the

ure

otor activit

A revealed

tion (F32,35

1) and a

increased

el A). Two

min) and

5 min). As

cond peak

levels we

conditions

he sampling

ng overall

physiologic

each param

with the v

which b

ere include

r collected

elation coe

inc., Chica

d a trend w

e behaviou

ty

d for the

52=19.6, ε=

significant

d immediat

peaks occ

another o

Table 1 s

k was imme

ere reache

s, rats sho

g period, w

inactivity o

cal and ho

meter at a

value of a d

both meas

ed therefore

d. All value

efficient. A

ago, IL, US

was accep

ural, phys

locomotor

=0.07, p<0

t time effe

tely after in

curred, one

ne when t

hows, the

ediately fo

ed already

owed no s

with their a

of these an

ormonal re

a certain tim

different p

surements

e using bin

es, over th

All analyse

SA). The le

pted at p<

iological a

activity re

0.001), a s

ect (F32,352=

nitiation of

e when the

the anima

highest pe

llowed by

5 - 10 m

significant

activity leve

nimals.

Novelty ex

esponses.

me point,

arameter a

s had a

n widths of

he differen

s were pe

evel of sign

0.10. Data

and horm

esponse a

ignificant t

= 20.8, ε=

novelty an

e animal w

al was plac

eak was a

low activity

in after ter

variation

els fluctua

xposure and

For these

as display

at correspo

correspon

f 5, 10 or 1

t time poin

erformed u

nificance w

a are pres

onal resp

a significa

treatment

=0.07, p<0

nd was sho

as placed

ced back

achieved a

y levels; st

rmination

in locomo

ating aroun

d the stress

e correlatio

yed in the

onding tim

nding time

15 min dep

nts, were

using SPS

was accepte

ented as m

onses to n

nt time*tre

effect (F1,1

0.001). Loc

ort-lasting

in the nov

in its hom

t t=5.8 ± 2

table basel

of novelty

otor activity

nd 0.4 coun

response

35

ons, the

graphs,

e point.

e point

pending

used to

SS 15.0

ed at p-

mean +

novelty

eatment

11=47.5,

comotor

(Figure

vel cage

me cage

2.5 min.

line and

. Under

y levels

nts/min,

Chapter

36

Heart r

For the

(F32,352=

a signi

increas

(Figure

controls

control

control

fluctuat

Blood p

The b

interact

p=0.26

novelty

after th

shows,

control

cage.

pressu

Millime

Body T

For the

(F32,352=

signific

interact

analyse

slight in

r 2

rate

e heart rate

=13.8, ε=0

ficant time

se in respo

e 1 panel

s, as show

levels we

conditions

ted closely

pressure

lood pres

tion (F32,35

) and a s

y induced

he animals

a maximu

levels we

Under con

re over th

etres of Me

Temperatur

e body tem

=1.6, ε=0.

ant time

tion effect

ed. Even t

ncrease fo

e response

0.2, p<0.00

e effect (F

onse to nov

B). The s

wn in Table

ere re-esta

s, heart ra

y around 34

ssure resp

52=3.2, ε=0

significant

a fast, sho

s were pla

um increas

ere reache

ntrol cond

he samplin

rcury (mm

re

mperature

1, p=0.20)

effect (F3

or treatm

though bo

or around 3

e, ANOVA

01), a signi

F32,352= 20

velty, start

significantly

e 1, was re

ablished 3

ate did not

40 beats p

ponse to

0.1, p=0.0

time effe

ort-lasting

aced in th

se was rea

d 15 - 20

itions, rats

ng period.

Hg).

response,

, no signifi

32,352= 10.

ent effect

dy temper

30 min sta

revealed a

ficant trea

.2, ε=0.2,

ting immed

y higher m

eached at

0 - 35 mi

vary signi

per min (bp

novelty s

018), no s

ect (F32,352

increase

e novel c

ached at t

min after

s did not

. Their blo

ANOVA re

icant treatm

.0, ε=0.1,

was found

rature is n

arting 0 –

a significan

tment effe

p<0.001).

diately afte

maximum

t=11.7 ± 3

n after ter

ificantly ov

pm).

showed a

significant

2=9.7, ε=0

in blood p

age (Figu

t=12.5 ± 3.

the anima

show sig

ood press

evealed no

ment effec

p<0.001)

d when on

not increas

5 min afte

nt time*trea

ct (F1,11=10

. Heart rat

er transfer

value as

3.5 min. Sta

rmination o

ver the sam

significan

treatment

0.1, p<0.00

pressure, s

re 1 pane

.2 min. Sta

al was retu

nificant va

sure fluctu

o time*trea

ct (F1,11=1.5

). Also, n

nly the rec

sed signific

er the anim

atment inte

0.2, p=0.0

te showed

to the nov

compared

able basel

of novelty

mpling per

nt time*tre

effect (F1

01). Expo

starting 0

el C). As T

able basel

urned to it

ariations in

ated arou

atment inte

5, p=0.245

no time*tre

covery peri

cantly, it s

mals were

eraction

09) and

d a fast

vel cage

d to the

ine and

. Under

riod and

eatment

1,11=1.4,

sure to

- 5 min

Table 1

ine and

s home

n blood

nd 110

eraction

5) and a

eatment

iod was

shows a

already

returne

shown

temper

experie

samplin

(°C).

Plasma

The pla

interact

p=0.02

corticos

novelty

higher

min. Pl

after te

corticos

control

variatio

around

ed to their

in Table

rature seem

enced by

ng period,

a Corticost

asma corti

tion (F16,17

9) and

sterone re

y exposure

maximum

lasma cort

ermination

sterone le

condition

on in plasm

36 ng/ml.

home cag

1, was

ms to incre

the exper

body tem

terone

icosterone

76=3.2, ε=

a signific

sponse ha

e was term

increase,

ticosterone

of novelty

evels fluctu

(t=92.5 an

ma cortico

ges (Figure

at t=32.5

ease slight

rimental a

mperature

response

=0.2, p=0.0

cant time

ad a slow

inated (Fig

as compar

e levels re

y exposure

uated slig

nd t=102.5

osterone, h

e 1 panel

± 3.7 m

tly, but not

animals pr

levels fluc

to novelty

033), a si

effect

increase, r

gure 1 pan

red to the c

eached bas

e. At 75 –

htly but n

min). Und

however n

Novelty ex

D). The m

min. Unde

t-significan

resent in t

ctuated ar

y showed

ignificant t

(F16,176=4.7

reaching s

nel E). As T

controls, w

seline and

– 85 min a

non-signific

der control

not signific

xposure and

maximum v

r control

tly, during

the same

round 37.7

a significa

treatment

7, ε=0.2,

significance

Table 1 sh

was achiev

d control le

after termi

cantly as

conditions

cant. Their

d the stress

value reac

conditions

novelty ex

room. O

7 Degree

ant time*tre

effect (F1

p=0.006

e 5 - 10 m

hows, a sig

ved at t=19

evels 20 -

nation of

compared

s, there wa

r levels flu

response

37

hed, as

s, body

xposure

ver the

Celsius

eatment

1,11=6.3,

6). The

min after

gnificant

.2 ± 4.2

25 min

novelty,

to the

as some

uctuated

Chapter

38

Act

ivity

(co

unts

/min

)

0

5

10

15

20

25

30H

ear

t ra

te (

bpm

)

320

360

400

440

480

Blo

od p

ress

ure

(mm

Hg)

100

110

120

130

140

Bod

y te

mpe

ratu

re (

°C)

37,0

37,5

38,0

38,5

39,0

Cor

ticos

tero

ne

(ng/

ml)

0

50

100

150

200

Figure (panel exposu10-min and nobaselinbetwee*p<0.05

r 2

-30 -1

A

B

C

D

E

1. Time couC), body te

ure. Data aremean value

ovelty-exposene period, theen the lines)5; (*)p<0.10.

5 0

*

*

* *

* *

urse of changmperature (p

e expressed es + SEM foed conditione 15 min ex) and the 2

15 30

**

*

*

**

* **

** *(*) (*)

ges in locompanel D) anas 5-min avr the cortico

n (closed syxposure to no2-h post-nove

Time

0 45

*

** *

motor activity d plasma coerages + SEsterone meaymbols, n=6ovelty or nonelty period.

(min)

60 7

(panel A), horticosteroneEM for the phasurements o). The respn-novelty coSignificance

5 90

eart rate (pae (panel E) ihysiological of the controonses are sntrol period e: novelty-ex

105 12

ContrNove

(*)

anel B), bloodn response measuremen

ol (open symshown for th(indicated b

xposed vers

20 135

*

rol (n=7)elty (n=6)

d pressure to novelty

nts and asmbols, n=7)

he 30-min y the area

sus control

Chang

The tim

under b

C respe

For w

(F10,110=

effect

signific

treatme

REM s

p=0.05

At base

betwee

baselin

and les

During

in wake

sleep. T

change

reache

t=5.0 ±

baselin

after te

wakefu

togethe

on REM

conditio

period.

es in slee

me course

both contro

ectively).

wakefulnes

=7.4, ε=0.

(F10,110=11

ant time*t

ent (F1,11=

sleep, an

9) was pre

eline, ther

en the co

ne period,

ss in wakef

the 15 min

efulness to

This lasted

es in respo

d at t=10.

± 2.5 and

ne levels w

ermination

ulness was

er with a s

M sleep. T

ons did no

ep-wake di

of change

ol and nov

s, ANOV

4, p<0.001

.0, ε=0.4,

treatment

12.5, p=0

almost s

esent and n

re were no

ontrol cond

animals sp

fulness (33

n of novelt

ogether wit

d until the

onse to no

0 ± 2.5 m

t=0.0 ± 5

were reache

of novelty

s slightly b

ignificant s

This lasted

t show any

istribution

es in the a

velty-expos

VA reveal

1), a signif

p=<0.001

interactio

.005) and

significant

no significa

o differenc

dition and

pent most

3.3 %) and

ty exposur

th a signifi

first 15 mi

ovelty were

min and the

5.2 min re

ed again fo

y. At 60 - 7

ut significa

slight incre

d only for t

y significan

n in respo

amount of

sed conditi

ed a si

ficant trea

1). Also fo

n (F10,110=

time effe

time*treat

ant time an

ces in time

d the nov

of the 15-

d REM slee

re, there w

cant reduc

n (t=22.5 m

e fast with

e minimum

espectively

or all three

75 min afte

antly reduc

ease in NR

this 15-mi

nt variation

Novelty ex

nse to nov

wakefulne

ons is illus

gnificant

atment (F1,

or NREM

=6.5, ε=0.

ect (F10,110

tment inte

nd treatme

e spent on

velty-expos

-min interv

ep (6.7 %).

as a signif

ction in tim

min) after

the maxim

m value for

y as show

vigilance

er terminat

ced for the

REM sleep

n interval.

n in vigilan

xposure and

velty expo

ess, NREM

strated in F

time*treat

11=16.7, p

sleep, AN

.4, p=0.00

=9.0, ε=0

eraction (F

nt effects w

n the three

sed condi

vals in NRE

ficant incre

me spent in

novelty ex

mum value

r NREM a

wn in Tabl

states betw

tion of nov

e novelty-e

duration a

The anim

ce states o

d the stress

osure

M and REM

Figure 2 (p

tment inte

p=0.002) a

NOVA sho

01), a sig

.4, p<0.00

F10,110=2.5,

were found

e vigilance

tion. Duri

EM sleep

ease in tim

NREM an

posure. Th

e for wake

and REM s

e 1. Cont

ween 15 –

velty (t=82

exposed co

and with n

mals under

over the sa

response

39

M sleep

panel A-

eraction

nd time

owed a

gnificant

01). For

ε=0.4,

d.

e states

ng this

(60 %),

me spent

nd REM

hus, the

efulness

sleep at

trol and

– 30 min

.5 min),

ondition

o effect

control

ampling

Chapter

40

Assoc

respon

Maximu

The ma

reache

plasma

separa

Table 1

RE

M s

leep

(m

in)

0

1

2

3

4

NR

EM

sle

ep

(min

)

0

5

10

15

Wak

efu

llne

ss (

min

)

0

5

10

15

Figure 2REM slefor the cn=6). Thcontrol Significa

r 2

iations b

nses

um/minimu

aximum va

d (TMAX) fo

a corticoste

tely and a

1.

-30 -15

A

B

C

2. Time coureep (panel Ccontrol condhe responsesperiod (ind

ance: novelty

etween t

um values

alue reach

or locomot

erone and

a group me

5 0

(*)

*

*

rse of changC) in responsition (open ss are shownicated by thy-exposed ve

he behav

reached w

ed (VMAX)

tor activity

wakefulne

ean was c

15 30

*

*

*

es in the amse to novelty symbols, n=7 for the basehe area beersus contro

vioural, p

with corresp

and the ti

, heart rat

ess duratio

calculated

Time (

0 45

mount of wakeexposure. D7) and for theline period, etween the l *p<0.05; (*)

physiologi

ponding tim

me point a

e, blood p

n were de

across the

(min)

60 75

efulness (paData are expr

e novelty-exthe 15 min elines) and )p<0.10.

cal, horm

me points

at which th

pressure, b

termined f

ese values

5 90

*

*

nel A), NREMressed as 15xposed condexposure to nfor the 2-h

monal and

his maximu

body tempe

for each in

s and is sh

NovelContr

105 12

M sleep (pan5-min averagition (closednovelty or no

post-novelt

d EEG

um was

erature,

dividual

hown in

lty (n=6)ol (n=7)

20 135

nel B) andes + SEM symbols,

on-noveltyty period.

For NR

reductio

the no

activity

(F1,11=6

minimu

was fou

temper

For the

TMIN va

blood p

Param

Act

HR

BP

BT

Cort

Wake

NREM

REM

Act: locorticoduratio

Table minuteshowndetermThe V(n=6). ± SEM

REM sleep

on occurre

velty-expo

(F1,11=49.

6.4, p=0.0

um value o

und for the

rature (F1,1

e novelty-e

alues differ

pressure, w

meter Re

Ma

Ma

Ma

Ma

Ma

Ma

M Mi

Mi

ocomotor actosterone; Waon. Significan

1. Maximumes (TMAX) for as a redu

mined for eacVMAX / VMIN is

The TMAX / TM.

duration a

ed for thes

osed and

6, p<0.001

028) and w

of NREM sl

e maximum

1=4.3, p=0

exposed co

red across

wakefulnes

esponse

ax

ax 3

ax 1

ax

ax

ax

n

n

tivity; HR: heake: wakefunce: novelty-

m value reacAct, HR, BP

ction occurrch individuals shown for TMIN is only s

and REM s

se measur

control co

1), heart ra

wakefulnes

leep durati

m values o

0.062).

ondition, it

the meas

ss duration

V

Contro

3.7 ± 1.2

373.6 ± 7.6

117.6 ± 3.3

38.1 ± 0.2

88.8 ± 12.6

8.1 ± 1.2

6.2 ± 1.1

0.0 ± 0.0

eart rate; BPulness duratiexposed ver

ched (VMAX) P, BT, Cort red for thes separately athe control

shown for the

sleep dura

res. Signifi

ondition for

ate (F1,11=4

ss duratio

ion (F1,11=2

of blood pr

t was furth

ured param

n, NREM s

VMAX / VMIN

l Nov

22.5 ±

454.8 ±

129.3±

38.7±

6 156.9±

15.0 ±

0.0 ±

0.0 ±

P: blood preion; NREM: rsus control *

and time poand Wake.

se measuresand a groupcondition (n

e novelty con

Novelty ex

tion the VM

cant differ

r the max

47.1, p<0.0

on (F1,11=2

25.8, p<0.0

ressure (F1

hermore a

meters. Lo

leep durat

velty

± 2.5* c

m

± 9.2* b

± 5.2(*) m

± 0.2(*) °

± 25.2* n

± 0.0* m

± 0.0* m

± 0.0 m

ssure; BT: bNREM slee

*p<0.05; (*)p

oint at whichFor NREM as. The VMAX

p mean was n=7) and forndition (n=6).

xposure and

MIN and TM

rences wer

ximum valu

001), plasm

26.7, p<0.0

001). A tre

1,11=3.7, p=

nalysed w

ocomotor a

ion and RE

counts/

min

bpm

mmHg

°C

ng/ml

min

min

min

body temperep duration;

p<0.10.

this maximand REM th

X / VMIN andcalculated ar the novelty. Values are

d the stress

IN are show

re found b

ues of loc

ma cortico

001) and

end to sign

=0.079) an

whether the

activity, hea

EM sleep d

TMAX / TMIN

Novelty

5.8 ± 2.5

11.7 ± 3.5

12.5 ± 3.2

32.5 ± 3.7

19.2 ± 4.2

10.0 ± 2.5

5.0 ± 2.5

0.0 ± 5.2

rature; Cort: REM: REM

um was reae VMIN and T

d TMAX / TM

across these y-exposed copresented a

response

41

wn as a

between

comotor

osterone

for the

ificance

nd body

e TMAX /

art rate,

duration

5 min

5 min

2 min

7 min

2 min

5 min

5 min

2 min

plasma M sleep

ached in TMIN are IN were values.

ondition as mean

Chapter

42

had a

maximu

respon

compa

The TM

activity

wakefu

the TMA

Correla

The co

locomo

corticos

on corr

all othe

levels a

The co

activity

signific

correla

(p=0.57

correla

pattern

r9=0.89

signific

duratio

tempor

The pa

heart

respect

correla

with pl

r 2

similar TM

um or min

ses were

red to all

MAX of cor

, heart ra

ulness dura

AX of body

ations betw

orrelation c

otor activi

sterone an

relations be

er physiolo

are reflecte

orrelation c

and hea

ant and w

tion coeff

7). Betwee

tion coeff

was signi

9 (p=0.001

antly corr

n indicatin

ral characte

attern of w

rate and

tively. Bet

tion coeffi

asma cort

MAX/TMIN m

imum valu

initiated to

other resp

rticosterone

ate and bl

ation, NRE

temperatu

ween respo

coefficients

ity, heart

nd wakeful

etween loc

gical respo

ed in the p

coefficient

rt rate, an

was r28=0.

ficient with

en plasma

icient was

ificantly co

1). Thus,

elated wit

ng that the

eristics.

wakefulnes

blood pre

tween wak

cient was

ticosterone

meaning th

ue around

ogether. Bo

ponses and

e did not

ood press

EM sleep d

re.

onses

s for the n

t rate, b

ness dura

comotor ac

onses, as

hysiologica

for the re

nd betwee

77 (p<0.0

h body te

corticoste

s found w

orrelated w

the locom

th that of

eir respons

ss duration

essure wi

kefulness

found wit

e was sign

hat these

the same

ody tempe

d was thus

differ sign

sure but w

duration an

novelty-exp

blood pre

tion are sh

ctivity, EEG

this will sh

al and horm

esponse p

en locomo

001) and r

emperature

erone and

with r14=0.

with the pat

motor activ

heart rat

ses over t

n was also

ith r9=0.97

duration a

th r9=0.33

nificant wit

responses

time point

erature had

s a slower

nificantly fr

was signif

nd REM sle

posed resp

ssure, bo

hown in Ta

G wakefuln

how to wha

monal resp

pattern ove

otor activity

r28=0.79 (p

e was no

locomotor

14 (p=0.6

ttern of wa

vity respon

te, blood

time to no

o significa

7 (p<0.00

and body

(p=0.39).

th r4=0.96

s to nove

ts, making

d a signific

r response

rom the T

ficantly hig

eep durati

ponse patt

ody temp

able 2. The

ess duratio

at extent be

ponses.

er time be

y and blo

p<0.001)

ot significa

r activity a

64). The l

akefulness

nse patter

pressure

ovelty expo

antly correl

01) and r9

temperatu

The corre

(p<0.001)

elty reache

it likely th

cantly high

e than the

TMAX of loc

gher than

on but low

erns over

perature,

e main foc

on respons

ehavioural

etween loc

od pressu

respective

ant with r

also no sig

ocomotor

duration a

n over tim

and wake

osure had

lated with

9=0.96 (p

ure, no sig

elation coe

). Thus, th

ed their

hat their

er TMAX

others.

comotor

that of

wer than

time of

plasma

cus was

ses and

activity

comotor

ure was

ely. The

r28=0.11

gnificant

activity

and was

me was

efulness

similar

that of

<0.001)

gnificant

efficient

he EEG

wakefu

of locom

that the

Behav

The rel

exposu

conditio

ANOVA

ε=0.6, p

time e

time*tre

signific

close t

time*tre

(F1,11=3

sniffing

p<0.00

effect (

ulness dura

motor activ

ese respon

ioural obs

lative dura

ure period

ons is show

A revealed

p<0.001),

effect (F2,2

eatment in

ant time*t

to significa

eatment in

39.7, p<0.0

g, ANOVA

1), a signi

(F2,22=103.

Table 2.over time

Act HR BP BT Cort Wake Act: loctemperaSignifica

ation respo

vity, heart

nses to nov

servations

ation of five

and the po

wn in Figur

d for immo

a significa

22=31.0, ε

teraction (

treatment

ant treatme

nteraction (

001) and a

showed a

ificant trea

.7, ε=0.6,

. Correlatione of Act, HR,

Act

1.000.770.790.110.140.89

comotor actature; Cort: ance: *p<0.0

onse patter

rate, blood

velty expos

s

e different

ost-novelty

re 3.

obility a si

ant treatme

ε=0.6, p<0

(F2,22=4.4,

interaction

ent effect

(F2,22=24.8

a significa

a significan

atment effe

p<0.001).

n coefficient BP, BT, CO

HR

0 7* 1. 009* 0.97*1 0.52*4 0.70*9* 0.97*

tivity; HR: hplasma co

05

rn over tim

d pressure

sure had s

behaviour

y period un

gnificant t

ent effect (

0.001). Fo

ε=0.8, p=0

n was fou

(F1,11=3.6,

8, ε=0.6, p<

ant time ef

nt time*trea

ect (F1,11=1

Post-hoc

for the novORT and Wak

BP

1.00 0.41* 0.68* 0.96*

heart rate; orticosterone

Novelty ex

e was sign

and plasm

imilar temp

rs for the b

nder both c

time*treatm

(F1,11=25.2

or consum

0.036) was

nd (F2,22=

, p=0.085)

<0.001), a

ffect (F2,22=

atment inte

116.0, p<0

analysis s

elty-exposedke (n=6).

BT

1.00 0.64* 0.33

BP: blood e; Wake: w

xposure and

nificantly co

ma corticos

poral chara

baseline p

control and

ment intera

, p<0.001)

mption, o

s found. Al

4.7, ε=0.8

). Rearing

a significan

=29.8, ε=0

eraction (F

.001) and

showed tha

d response

Cort W

1.00 0.96* 1

pressure; Bakefulness

d the stress

orrelated w

sterone, ind

acteristics.

period, the

d novelty-e

action (F2,2

) and a sig

nly a sig

so for groo

8, p=0.03)

had a sig

nt treatmen

0.6, p<0.00

F2,22=107.2

a significa

at the beh

patterns

Wake

1.00

BT: body duration.

response

43

with that

dicating

novelty

exposed

22=27.3,

gnificant

gnificant

oming a

with a

gnificant

nt effect

01). For

, ε=0.6,

ant time

haviours

Chapter

44

during

experim

immob

time. O

for 1.3%

periods

observa

Novelty

increas

0.3%)

reductio

were be

During

conditio

0.0 ± 0

immob

towards

novelty

were st

r 2

the basel

ment was

ile behavio

Other beha

% of the ti

s was foun

ation perio

y exposur

se in sniffin

and in gro

on in immo

ehavioural

the first 2

on, an incr

0.0%) and

ility (41.0 ±

s baseline

y as compa

till behavio

line period

performed

our was p

aviours that

ime. Unde

nd, indicati

od.

re induced

ng (66.3 ±

ooming (1

obility (0.4

lly active d

20 min aft

rease in sn

grooming

± 10.2 % v

levels aga

ared to the

ourally activ

d did not

d during th

primarily se

t were pre

r control c

ing that th

d, as com

± 6.3% vs.

8.2 ± 6.2%

± 0.4% vs

uring expo

ter this ex

niffing (11.7

(18.0 ± 2.

vs. 93.3 ± 2

ain. Consu

e control c

ve during t

differ bet

he resting

een during

esent were

conditions,

hese anima

mpared to

. 1.5 ± 1.4

% vs. 2.6

s. 84.3 ± 1

osure to no

xposure to

7 ± 1.6% v

5% vs. 4.4

2.5%) was

umption oc

ondition (1

the first 20

ween the

phase (lig

g this base

grooming

no signific

als were im

the cont

4%), in rea

± 1.4%),

1.8%). Thi

ovelty.

novelty, a

vs. 0.5 ± 0.2

4 ± 2.0%)

s still visibl

ccurred spe

19.0 ± 9.2%

min after t

two cond

ght period

eline perio

for aroun

cant differe

mmobile d

rol condit

aring (9.2

together

is indicates

as compar

2%), rearin

together w

e even tho

ecifically a

% vs. 0 ± 0

termination

ditions. Sin

d) of the a

od for 89%

d 7% and

ence betw

uring mos

ion, a sig

± 1.6% vs

with a sig

s that the a

red to the

ng (1.5 ± 0

with a redu

ough levels

fter termin

0%). The a

n of novelt

nce the

animals,

% of the

sniffing

een the

st of the

gnificant

s. 0.4 ±

gnificant

animals

control

0.7% vs.

uction in

s did go

ation of

animals

y.

DISCU

In the p

simulta

undistu

measu

physiol

observa

signific

room.

animals

addition

under

period.

affected

Figure observaand novt=-5 minthe animwhen th

Con

trol

(n

=7)

Nov

elty

(n

=6)

SSION

present stu

aneously a

urbed hom

rements u

ogical val

ation perio

antly, afte

It is uncle

s in the sa

n, EEG vi

control co

Altogethe

d by the

3. Relativeation time) fovelty-exposen), the novelmal is placedhe animal is r

Baseline

20 min

udy, behav

and contin

me cage

nder undis

ues togeth

od. Only b

r novelty e

ar whethe

me room b

gilance st

onditions w

er, this indi

sampling

e duration (tor consumptid (n=6) condlty exposured in the novereturned to it

e

vioural, phy

nuously m

conditions

sturbed ho

her with lo

body temp

exposure

r this is ca

because it

ates and

were mainl

icates that

procedure

time spent ion, groomindition. Data or non-noveel cage) andts home cage

Novelty ex

15 m

ysiological,

measured

s and afte

ome cage

ow cortico

perature s

experience

aused by

is not refle

behavioura

y inactive

t under co

es, nor s

on the behng, immobilityare shown foelty control p

d the post-noe). Data are

xposure

in

Novelty ex

, hormonal

in freely

er brief n

conditions

osterone le

seemed to

ed by the

the prese

ected in an

al observa

and aslee

ntrol cond

ignificantly

havior exprey, rearing anor the baselperiod (15 movelty period presented as

Pos

2

xposure and

l and EEG

moving

novel cage

showed n

evels throu

increase

other anim

nce of the

ny of the o

ations show

ep during

itions, anim

y by the

essed as pnd sniffing ofine period (2

min; starting i(20 min; sta

s means.

st-novelty

20 min

d the stress

paramete

rats both

e exposur

normal and

ughout the

slightly, b

mals in the

e novelty-e

ther meas

wed that a

the exper

mals were

novelty ex

ercentage of the control 20 min; t=-25immediately arting immed

Immo

SniffiReari

GrooCons

response

45

ers were

under

re. The

d stable

e entire

but not-

e same

exposed

ures. In

animals

rimental

neither

xposure

of the (n=7)

5 until when

diately

obility

nging

mingsumption

Chapter

46

experie

data ar

N

increas

locomo

activitie

accorda

novel e

Gaglian

locomo

presen

novelty

explorin

and sta

not cau

this be

animals

exposu

C

hormon

heart r

and HP

respon

The lat

signific

increas

parame

blood p

followin

that SA

have im

the hea

1992).

r 2

enced by t

re of high q

Novelty ex

se in behav

otor activity

es such as

ance with

environmen

no et al.,

otor activity

ce of slee

y. Behaviou

ng and inc

arted to co

use total h

haviour ex

s were be

ure and fro

Concomita

nal respon

rate, blood

PA axis a

se to nove

tter is part

antly incre

se under

eters show

pressure s

ng the incre

AM system

mmediate e

art and in

The cortic

the other a

quality and

xposure w

vioural acti

y and the b

s sniffing a

other stud

nt (Feenst

2008). W

y rapidly

p initiation

ural observ

creased tim

nsume foo

horizontal b

xplaining th

ehaviourall

m then on

ant with the

ses to nov

pressure

activation.

elty expos

tly related

ease under

novelty-ex

wed differen

showed an

ease in be

m activatio

effects on t

ducing va

costerone

animals in

are withou

was assoc

ivity. The

behavioura

and rearin

ies showin

tra and Bo

When the

declined t

was obse

vations sh

me spent

od and wat

body move

he observe

ly active u

displayed

ese behav

velty. Nove

and plasm

On avera

ure as we

to the fac

r control co

xposed co

nt time cou

acute and

ehavioural a

on results

the cardiov

sodilatatio

response

the same

ut stress-c

ciated with

telemetry

al observat

ng, but als

ng increase

otterblom, 1

animals w

towards lo

erved durin

owed that

immobile.

ter. Since g

ement, the

ed low lev

until 15 -

normal lev

vioural acti

el cage ex

ma cortico

age body

ell but this

ct that bod

onditions a

onditions

urses in res

d rapid inc

activity. Th

in the rap

vascular sy

n (Axelrod

showed a

e room. Th

confounding

h a compl

recordings

tions revea

o in groom

ed arousal

1996; De G

were retur

ow levels

ng the first

the anima

Moreover

grooming a

e radiotele

vels of loco

20 min a

vels of slee

vity levels

posure ind

sterone, in

temperatu

did not re

dy tempera

as well. Th

to reach

sponse to

crease in r

his is in agr

pid release

ystem ther

d and Reis

a slower o

his shows

g effects.

lete lack

s showed a

al an incre

ming. Thes

during exp

Groote and

rned to th

within 5 m

t 15 min af

als reduced

r, the anim

and eating

metry set-

omotor act

after termi

ep.

were the

duced temp

ndicating b

ure showed

each statis

ature show

his may ha

significan

novelty. Bo

response t

reement w

e of catec

reby increa

sine, 1984

onset, reac

that the o

of sleep

a rapid incr

ase in exp

se findings

posure of r

d Linthorst

heir home

min, howe

fter termin

d their tim

mals still g

g/drinking o

-up did no

tivity. Ove

nation of

physiologi

poral incre

both SAM

d an incre

stical signif

wed a slig

ave preven

nce. The

oth heart r

to novelty,

with the kno

holamines

asing the o

4; Johnson

ching sign

obtained

and an

rease in

plorative

s are in

rats to a

t, 2007;

cages,

ever, no

ation of

e spent

roomed

often do

t detect

rall, the

novelty

ical and

eases in

system

ease in

ficance.

ght non-

nted the

various

rate and

closely

owledge

s, which

output of

n et al.,

ificance

when t

increas

result o

(Axelro

observe

result

vasoco

achieve

corticos

pressu

respon

exposu

all mea

show t

levels,

with a

animal,

The ma

duratio

what ex

respon

and the

indicati

wakefu

pressu

temper

activity

novelty

reliable

locomo

pressu

related

suppor

the anima

se in beha

of a neuroe

od and Reis

ed slight

of an inc

onstriction.

ed for the

sterone we

re, wakefu

ses were

ure, the tim

asures rea

that the re

whereas

delay. Be

, reliable c

ain focus

n and all

xtent beha

ses. Signif

e heart ra

ng that

ulness dura

re pattern

rature resp

, which m

y exposure

e indicator

otor activit

re and als

to ongoi

rt for the b

als were a

avioural ac

endocrine c

sine, 1984

increase i

crease in

The calc

e novelty-

ere delaye

ulness du

most like

me courses

ached stab

ecovery of

heart rate

ecause all

correlation

was on co

other phy

avioural act

ficant corr

ate, blood

these had

ation was

n, and als

ponse wa

may have b

e. As has

of ongoing

ty respons

so plasma

ng behav

behaviour

already ret

ctivity with

cascade o

4; Johnson

n body te

metaboli

culated tim

exposed c

ed. Furthe

ration, NR

ely initiate

s of the phy

ble baselin

blood pre

e, body tem

measurem

analysis o

orrelations

ysiological

tivity levels

relations b

pressure a

d compar

also signif

so with th

s not cor

been caus

been disc

g behaviou

se. Theref

corticoster

ioural acti

that was

turned to

h a delay.

f HPA axis

et al., 199

emperature

sm, in m

me points a

condition

rmore, the

REM sleep

ed togethe

ysiological

e and con

essure clos

mperature

ments wer

of the respo

between

and horm

s are reflec

etween the

and wakef

rable resp

ficantly cor

he plasma

rrelated si

sed by the

cussed, the

ural activit

fore, we c

rone respo

vity and c

induced b

Novelty ex

their hom

Corticoste

s activation

92). Such a

e. Body te

muscle act

at which t

confirm th

e locomoto

p duration

er. Upon

and horm

ntrol levels

sely follow

and plas

re taken s

onse patte

locomotor

monal respo

cted in the

e locomoto

fulness du

ponses ov

rrelated wi

a corticos

gnificantly

e non-signi

e duration

ty during th

conclude

onses to n

can thus

by novelty

xposure and

me cages

erone secr

n, and is no

a delay is a

emperature

tivity and

the maxim

hat body

or activity,

and REM

terminatio

monal respo

s within 30

wed the be

ma cortico

simultaneo

erns over ti

r activity, E

onses, as

physiolog

or activity

uration pat

ver time.

ith the hea

sterone pa

with ong

ificant incr

n of wakef

he recover

that the h

ovelty exp

be consid

exposure

d the stress

and follow

retion is t

ot a fast re

also visible

e increase

from pe

mum chang

temperatu

heart rate

M sleep d

n of nove

onses diffe

0 min. The

ehavioural

osterone f

usly in the

ime was p

EEG wake

this will s

ical and ho

response

tterns were

The pat

art rate an

attern. The

going beha

rease foun

fulness is

ry phase t

heart rate

posure are

dered the

(Koolhaas

response

47

wed the

he final

esponse

e for the

es as a

eripheral

ge was

ure and

e, blood

duration

el cage

ered but

results

activity

followed

e same

ossible.

efulness

show to

ormonal

pattern

e found

tern of

d blood

e body

avioural

nd upon

a more

han the

, blood

closely

normal

s et al.,

Chapter

48

2011).

neither

cycle u

Gugten

et al., 2

G

environ

and the

explore

presen

when r

almost

novel c

co-wor

can ha

in a no

period,

reduce

well (va

may als

consum

interpre

(Morley

activity

metabo

I

and ho

behavio

ongoing

interpre

assess

non-co

differen

r 2

Indeed, th

r exceed t

under home

n, 1987), n

2011).

Gagliano a

nment is th

e motivatio

ed the nov

t for aroun

returned to

half of the

cage expos

kers studie

ve anothe

ovel cage s

suggestin

arousal fo

an Erp et

so have ha

mption of fo

eted as str

y et al., 1

during n

olic require

In conclus

rmonal res

oural activ

g behavio

etation. Th

sment of be

nfounding

nt stress va

he physiol

he averag

e cage con

or do they

and co-wor

he result o

on to explo

vel cage a

nd 75% of t

o their hom

e observed

sure and is

ed the gro

r function a

steadily in

ng that gro

ollowing s

al., 1994)

ad a main

ood and w

ress-induce

983; Dallm

novelty ex

ements as

ion, the pr

sponses in

vity of the a

ur seems

he present

ehavioural

conditions

ariables in

ogical and

ge values

nditions (B

reach valu

rkers sugg

of the intera

ore it (Gag

as reflecte

the time. A

me cages

d time. Als

s thought t

oming res

as well (va

creased th

ooming is

tressors b

. Since ou

function f

water specif

ed feeding

man et al

xposure m

well.

resent resu

n rats are c

animals. A

to be mo

study also

, physiolog

s. It shows

associatio

d hormona

observed

Buttner and

ues related

gest that th

action of fe

gliano et a

ed in high

Animals sti

(around

so some gr

to be a str

ponse to n

an Erp et a

heir groom

not only a

but may ha

ur experim

for the anim

fically occu

g, as has b

l., 2006).

may have

ults show t

closely rela

An interpret

ore approp

o emphasi

gical and h

s the impo

on with beh

al values d

during the

d Wollnik,

d to volunta

he behavio

ear genera

l., 2008).In

levels of

ll showed

13% of th

rooming w

ress-reduc

novel cage

al., 1994).

ming behav

an immedi

ave a dela

ent involve

mal to clea

urred after

been repor

However,

induced

that the no

ated to the

tation in te

riate than

izes the ad

hormonal p

ortance of

havioural a

during nov

e active ph

1982; De

ary wheel r

our of the a

ated by the

n our stud

sniffing an

some exp

he time) bu

was presen

ing behavi

e exposure

They foun

viour during

iate respo

ayed resto

ed brief ha

an and cor

novelty ex

rted after s

the incre

some fee

ovelty-indu

ongoing, m

erms of me

the frequ

dded value

parameters

studying th

activity mea

velty expos

hase of ci

Boer and v

running (B

animals in

e unknown

y, animals

nd some

lorative be

ut were im

nt during an

iour. Van E

e and sugg

d that rats

g the obse

nse neces

rative func

andling, gr

rrect its fur

xposure. It

stressful sit

ased beha

eding to b

uced physi

mainly exp

etabolic su

ently used

e of simult

s under con

he time co

asurement

sure do

ircadian

van der

oersma

a novel

n space

s mainly

rearing,

ehaviour

mmobile

nd after

Erp and

gest this

s placed

ervation

ssary to

ction as

rooming

r. Some

t can be

tuations

avioural

balance

ological

plorative

pport of

d stress

taneous

ntrolled,

ourse of

s.

ACKNO

The au

their te

OWLEDGE

uthors wou

chnical as

EMENTS

uld like to t

sistance a

thank Leen

nd Helena

n Raeymae

a Geys for s

Novelty ex

ekers and

statistical a

xposure and

Gerd van

assistance

d the stress

den Kiebo

e.

response

49

oom for

Chapter 3

Simultaneous assessment of behavioural, physiological and hormonal responses to acute gentle

handling sleep deprivation in rats

W. Beerling1, 2, J.M. Koolhaas2, A. Ahnaou1, P. Meerlo2 and

W.H.I.M. Drinkenburg1

1 Department of Neuroscience, Janssen Research & Development, a division of

Janssen Pharmaceutica N.V., Turnhoutseweg 30, 2340 Beerse, Belgium; 2 Department of Behavioural Physiology, University of Groningen, Nijenborgh 7, 9747 AG

Groningen, The Netherlands

Chapte

52

ABSTR

Even th

activate

(HPA) a

deprivat

parallel.

with be

Another

samplin

study a

sympath

rats. Als

automa

stress p

used. D

between

pressur

showed

tempera

heart ra

corticos

min of t

sleep de

control

locomot

corticos

Altogeth

neuroen

related

method

activity

we conc

has a m

er 3

RACT

hough litera

es both the s

axis, there

tion studies

. Moreover,

haviour ma

r shortcomi

ng or sleep

aimed to ta

hetic and H

so, locomot

ted blood s

parameters

Detailed tim

n changes

re, body tem

d that durin

ature and p

ate and bloo

sterone, leve

the dark pe

eprivation p

values wit

tor activity

sterone res

her, we con

ndocrine an

to the phy

. Since a

response w

clude that 4

minor impact

ature exists

sympathico

are still sh

s are often

, we feel tha

ay strengthe

ing in rode

deprivation

ake physiolo

HPA axis ac

tor activity

sampling sy

in freely m

me and co

s in behav

mperature)

ng sleep de

plasma cor

od pressure

els compara

riod preced

procedure, t

thin 40 mi

response

sponse wa

nclude that

nd physiolog

ysical activit

close disso

was visible,

4-h sleep de

t on the ani

s that supp

o-adrenome

hortcomings

limited in t

at the analy

en the inter

ent sleep de

methods. T

ogical and

ctivity, durin

levels were

ystem for fr

moving rats

rrelational

vioural (loc

and hormo

eprivation m

rticosterone

e as compa

able to or s

ding sleep d

the respons

n. Correlat

patterns ov

as only co

short sleep

gical stress

ty that was

ociation be

, and since

eprivation p

mal.

ports the ge

edullary (SA

s in the pre

the possibil

ysis of the a

rpretation of

eprivation s

Taking into

hormonal

ng and after

e measured

requent and

s under con

analysis w

comotor ac

onal (cortico

mild tempor

were indu

red to the n

slightly below

deprivation w

ses showed

tional analy

ver time w

orrelated w

p deprivatio

s systems. T

s induced b

tween the

all measu

per se, as in

eneral hypo

AM) system

esent state

ity to take

activation of

f the conse

studies is t

account the

measureme

r 4-h gentle

d. Radiotele

d simultane

ntrolled, no

were used t

ctivity), phy

osterone) s

ral increase

uced with a

non-deprive

w normal w

were mainta

d different ti

ysis showe

were correla

with locomo

on mildly af

This stress

by our gen

physiologic

rements sta

nduced by o

othesis tha

and the hyp

e of knowle

multiple rea

f the stress

equences of

the use of

ese shortco

ents, in pa

e handling s

emetry in c

eous measu

n-confound

to determin

ysiological

stress param

es in locom

a tendency

ed control co

waking level

ained. Upon

me courses

ed that all

ated among

otor activity

ffects the b

system act

tle-handling

cal/hormona

ayed within

our gentle h

t sleep dep

pothalamic-

edge. Rode

ad-outs of s

systems in

f sleep dep

stress-conf

omings, the

arallel, indic

sleep depriv

ombination

urement of

ing conditio

ne the rela

(heart rate

meters. The

motor activit

for an incr

ondition. Ex

s during the

n terminatio

s but all ret

physiologi

g each oth

y and hea

basal activit

tivation was

g sleep dep

al and beh

n the norma

handling pro

privation

-pituitary

nt sleep

stress in

n concert

privation.

founding

present

cative of

vation in

with an

multiple

ons was

ationship

e, blood

e results

ty, body

rease in

xcept for

e last 30

on of the

urned to

ical and

her. The

art rate.

ty of the

s closely

privation

havioural

al range,

ocedure,

INTRO

The ne

homeo

the sy

adrena

(Akerst

al., 199

al., 200

animal

indicati

Spiege

Meerlo

system

(Akerst

effects

function

adverse

of the s

W

depriva

state o

often li

reviewe

depriva

system

read-ou

sympat

an imm

heart a

pressu

temper

axis ac

ODUCTION

euroendocr

stasis. Act

ympathico-

al (HPA) a

tedt and Fr

99; Spiege

06; Meerlo

studies f

ve of HPA

el et al., 19

et al., 20

m activation

tedt and F

on a b

ning and m

e consequ

stress syst

While lite

ation activa

of knowled

imited in t

ed by Me

ation affect

ms simultan

uts where

thetic and

mediate eff

and induci

re (Axelro

rature leve

ctivation a

N

rine stress

tivation of

adrenome

axis, has

roberg, 19

el et al., 19

o et al., 200

found inc

A axis act

999; Chapo

008). Furth

n, have b

roberg, 19

ehavioural

metabolic f

uences of s

ems.

rature exi

ates stress

ge (Meerlo

the possib

eerlo and

ts either th

neously (M

eas addit

HPA axis

fect on the

ng vasodi

od and R

els can incr

as well. B

s systems

the two m

dullary (S

been foun

979; von Tr

999; Chapo

08). Moreo

reased co

tivation (vo

otot et al.,

hermore, h

been foun

979; Irwin e

l, emotion

function. F

sleep depr

ists that

s systems,

o et al., 2

bility to ta

co-worke

he SAM sy

Meerlo et al

ional phy

activity. F

cardiovas

latation re

Reisine, 19

rease indir

Body temp

Sleep

are thoug

most impo

SAM) syst

nd during

reuer et al.

otot et al.,

over, durin

ortisol and

on Treuer

2001; Hip

higher cate

d during

et al., 1999

nal, cogni

For these r

rivation are

supports

there are

2008). Slee

ke multiple

rs, most

ystem or th

l., 2008). A

ysiological

or exampl

scular syste

esulting in

984; John

rectly as a

perature le

p deprivat

ght to play

rtant neuro

tem and

wakefulne

., 1996; Su

2001; Hip

ng sleep de

d corticos

et al., 19

polide et al

echolamine

wakefulne

9). Stress

tive, phys

easons, it

e mediated

the gene

still some

ep depriva

e read-ou

studies ju

he HPA ax

Also, most

read-outs

e, catecho

em thereb

an increa

son et a

a result of b

evels chan

tion and th

y an impor

oendocrine

the hypot

ess as co

uchecki et

polide et al

eprivation,

terone lev

996; Suche

., 2006; Sg

e levels, i

ess as co

hormones

siological,

is thought

d by chang

eral hypot

shortcomin

ation studie

ts of stres

ust focuse

is instead

studies on

s are al

olamines a

y affecting

se in hea

l., 1992).

both SAM

nge upon

he stress r

rtant role i

e stress sy

thalamic-p

ompared to

al., 1998;

l., 2006; S

most hum

vels respe

ecki et al.

goifo et al

ndicative o

mpared to

have a va

hormonal

t that some

ges in the

hesis that

ngs in the

es in anim

ss in para

d on how

of looking

nly take ho

so indica

are known

g the outpu

rt rate and

Moreover

system an

changes

response

53

n sleep

ystems,

pituitary-

o sleep

Irwin et

goifo et

man and

ectively,

., 1998;

., 2006;

of SAM

o sleep

ariety of

l, brain

e of the

activity

t sleep

present

mals are

allel. As

w sleep

at both

ormonal

ative of

to have

ut of the

d blood

r, body

nd HPA

in e.g.

Chapte

54

metabo

sympat

is know

Therefo

behavio

depriva

analysi

the int

Koolha

activati

behavio

situatio

physiol

A

confou

stressfu

room a

to take

in itsel

wakefu

imposs

loss pe

reduce

T

detail h

system

sleep lo

(McKen

sleep d

gentle

signific

habitua

2006; V

er 3

olism, mus

thetic and

wn, studie

ore, a sho

oural, phy

ation within

s of the ac

terpretation

aas and co

on may cl

oural activ

on can b

ogical/horm

Another s

nding sam

ul in them

and handle

measurem

lf. In orde

ulness is re

sible to exc

er se in rod

confoundi

Taking into

how 4-h ge

ms. Four to

oss with s

nna et al.

deprivation

handling

antly redu

ation to han

Van der B

scle activit

HPA axis a

es thus fa

ortcoming i

ysiological

n the sam

ctivation of

n of the

o-workers

losely refle

vity rather t

be consid

monal and

shortcomin

mpling meth

mselves. E.

e the anima

ments. Mor

er to keep

equired, w

clude the a

dent sleep

ing outcom

o account

entle handl

six hours o

significant

, 2008). P

n procedu

sleep dep

ce sleep t

ndling is in

orght et a

ty and pe

activity (Ax

ar hardly

n the pres

and horm

me animal

f the stress

conseque

(Koolhaas

ect the me

than the s

ered truly

d behaviou

g in rode

hods. The

.g. often th

als or the a

reover, als

p animals

which may

activation

deprivatio

mes.

these sho

ing sleep d

of sleep de

increases

Possible st

re were s

privation m

times and

ncluded (G

l., 2006; H

eripheral v

xelrod and

measure

sent state

monal stre

and how

s systems i

nces of s

s et al., 2

etabolic an

stressfulnes

y stressfu

ral activity

ent sleep

methods u

he experim

animal is t

so the slee

awake, s

activate t

of the stre

on studies,

ortcomings

deprivation

eprivation

in sleepin

tress-confo

significantly

method wa

is conside

rassi-Zucc

Hagewoud

asoconstri

Reisine, 1

different p

of knowle

ess read-o

these are

in concert

sleep dep

2011), neu

d physiolo

ss of a situ

ul when

response

deprivatio

used to ta

menter has

ransferred

p deprivati

some sort

he stress

ess system

these fact

s, the prese

n affects th

in rats hav

ess for up

ounding ef

y reduced

as used. T

ered a mild

coni et al.,

et al., 201

ction that

1984) Even

parameters

edge exists

outs are a

e correlate

with behav

privation. A

uroendocrin

ogical dem

uation. Th

dissociatio

occurs.

on studies

ke measur

s to enter

d to a differ

ion method

of stimul

systems.

ms by othe

tors should

ent study

e basal ac

ve shown to

p to 3 h aft

ffects of t

in this st

This metho

d procedu

1993; Gra

10). Habitu

may resu

n though a

s simultan

s on how

affected by

ed. Moreov

viour can f

As discus

ne stress

mands requ

ey sugges

on betwe

s is the

rements ar

the exper

rent cage

d used is s

ation and

Even thou

r factors a

d be minim

aimed to s

ctivity of the

o lead to a

fter its term

the sampli

tudy. Here

od has sh

re when p

assi-Zuccon

uation to h

ult from

ll of this

neously.

multiple

y sleep

ver, the

facilitate

sed by

system

uired for

st that a

en the

use of

re often

rimental

in order

stressful

forced

ugh it is

as sleep

mized to

show in

e stress

an acute

mination

ing and

eto, the

hown to

previous

ni et al.,

handling

will red

handlin

we use

Greene

samplin

Abelso

parame

these m

(locomo

hormon

the rec

investig

system

METHO

Anima

At the

Horst, T

were in

cages

and wa

home c

up (Da

samplin

also d

temper

light/da

experim

duce the e

ng used to

ed radiotele

e et al., 2

ng system

n et al., 20

eters in fre

methods, t

otor activit

nal (cortico

covery the

gate the a

m in respon

ODS

ls and hou

beginning

The Nethe

ndividually

(43x27x39

ater ad libi

cage in the

ataScience

ng system

daily hand

rature (21

ark regime

mental prot

extent of H

keep the

emetry (Gu

007; Tang

m (Steffens

005) for fre

eely moving

the effect o

ty), physiol

osterone)

reof. Deta

activity of

se to acute

using

g of the e

erlands), w

housed f

9 cm) cont

itum. Imm

e experime

es Interna

m (AccuSam

dled for w

± 1°C), c

e using a 3

tocols were

HPA axis

animals a

uiol et al.,

g et al., 2

s, 1969; T

equent an

g rats unde

of short-ter

logical (he

stress par

ailed time

the class

e sleep de

xperiment,

weighing 31

for at leas

taining bed

ediately af

ental set-up

ational, St.

mpler Mic

weighing

controlled

30-min ris

e approved

Sleep

and adren

awake (Dob

1992; Van

007) in co

Thrivikram

d simultan

er controlle

rm, 4-h sle

art rate, bl

rameters w

and corre

sical neuro

privation a

, 18 adult

10-330 g a

st two wee

dding, cag

fter surger

p. This set

. Paul, M

ro, DiLab,

purposes.

humidity

e and dim

d by the lo

p deprivat

nalin activa

brakovova

n den Buus

ombination

an et al.,

neous mea

ed, non-co

eep depriv

lood press

was studie

lational an

oendocrine

and to inter

male Spr

at the time

eks prior t

ge enrichm

ry, each a

t-up consis

MN, USA)

Lund, Sw

The roo

(50 ± 10%

m period w

cal ethical

tion and th

ation caus

a et al., 19

se, 1994;

n with an

2002; Ro

asurement

nfounding

vation in ra

sure, body

d, in para

nalysis wa

e and phy

rpret the st

rague-Daw

of surgery

o surgery

ment and s

nimal was

sted of a ra

and an

weden). An

om was k

%) and a

with lights

committee

he stress r

sed by the

93). Furthe

Leon et al

automated

oyo et al.

of multiple

conditions

ats on beha

temperatu

llel, togeth

as used to

ysiological

tressfulnes

wley rats (

y were use

in polyca

standard ra

s placed w

adioteleme

automated

nimals we

kept at c

fixed 12

on at 06.0

e.

response

55

e gentle

ermore,

., 2004;

d blood

, 2004;

e stress

s. Using

avioural

ure) and

her with

further

l stress

ss.

(Harlan,

d. They

rbonate

at chow

within its

etry set-

d blood

ere then

constant

: 12 h

00h. All

Chapte

56

Surger

Surgery

Piritram

subcuta

activity

C50-PX

to the

pressu

two bio

the sku

at 3 m

were a

jugular

sample

Thrivikr

with the

led sub

dorsal

and co

machin

connec

the cat

start of

Experi

In total

to eithe

William

window

to both

sleep-d

er 3

ry

y was pe

mide (dipid

aneously

, heart rat

XT, DataS

abdomina

re cathete

opotential

ull and the

m on eithe

nchored to

vein cath

es to be

raman et a

e tip of the

bcutaneou

region of

onnected e

ne (AccuS

cted to a c

heter open

f the exper

mental de

12 animal

er control

ms design w

w. Due to b

h condition

deprived c

erformed

dolor, 0.02

at the sta

te, blood

ciences In

al wall to

r of the tra

leads for

bare ends

er side lat

o the skull

heter (pol

collected

al., 2002).

e catheter r

sly throug

the neck.

either to th

Sampler M

continuous

n. The anim

iments.

esign

ls survived

or sleep

with 3 days

blocked blo

ns. This re

condition b

under O2

25 mg/kg,

art of surg

pressure,

nternationa

ensure s

ansmitter w

cortical EE

s of these

teral to the

with screw

yurethane

in freely

The cathe

reaching th

h a Dacro

The cathe

he infusion

Micro; DiLa

infusion o

mals were

d surgery. A

deprivatio

s in betwee

ood sampl

esulted in

but not wit

2-N2O-isof

0.1 ml/10

gery. A tra

body temp

al) was imp

stabilization

was inserte

EG measu

electrodes

e midline a

ws and den

; ID: 0.36

moving r

eter was i

he entrance

on button

eter was co

n pumps

ab). After

of saline +

allowed to

After recov

n conditio

en session

ing cathete

n=7 for th

th the sam

lurane an

00 g body

ansmitter

perature a

planted int

n (Greene

ed in the f

urements w

s were plac

and 6 mm

ntal cemen

6, OD: 0.

rats was i

nserted th

e of the rig

that was

onnected t

or to the

surgery,

heparin (1

o recover fo

very from s

ns using a

ns and usin

ers, some

he control

me anima

naesthesia

y weight) w

to record

and cortica

traperitone

e et al., 2

femoral art

were led s

ced in con

m posterior

nt. In addit

84, DiLab

implanted

rough the

ght atrium.

attached t

through a

automated

animals w

10 IU/ml; 0

or at least

surgery, ra

a balance

ng a standa

animals w

condition

als present

. The an

was admin

gross loc

al EEG (T

eally and a

2007). The

tery. Furthe

subcutaneo

ntact with t

to bregma

tion, a dua

b) allowing

(Steffens

right jugu

The cathe

to the skin

spiral to a

d blood sa

were imme

0.24 ml/h)

two weeks

ats were su

d and cro

ard circadi

were not su

and n=7

t in both

nalgesic

nistered

comotor

L11M2-

attached

e blood

ermore,

ously to

he dura

a. They

al tubing

g blood

, 1969;

lar vein

eter was

n in the

a swivel

ampling

ediately

to keep

s before

ubjected

oss-over

ian time

ubjected

for the

groups.

Seven

behavio

measu

automa

first ha

were c

connec

transm

a 30-m

followe

control

depriva

Sleep d

Total s

accord

2006).

signs o

lifted fr

wakefu

1993).

Therefo

further

undistu

least 1

conditio

the sam

set-ups w

oural, phy

red contin

atically and

alf of the li

carefully av

cting them

itters. Tele

min and 20

ed for all m

period sta

ation recov

deprivatio

leep depri

ing to pub

The anima

of sleep. O

rom its cag

ulness for a

Sleep dep

ore, sleep

referred to

urbed. In o

10 min on

ons, anima

me experim

were used

ysiological

nuously a

d repeated

ight phase

voided. Th

m to the a

emetric rec

0-min bas

measureme

arting at th

very phase

on

vation was

blished me

al was stro

nly when t

ge for a fe

at least 80

privation wa

deprivation

o as 4 h. I

order to ha

n the two

als were le

mental room

d in para

and ele

and autom

ly. All expe

e, i.e. the

he experim

automated

cordings an

seline perio

ents by a 4

e lights-on

.

s started a

thods (Gra

oked on its

this did not

ew seconds

0% of the

as termina

n actually

Immediate

abituate the

o days pre

eft undistu

m.

Sleep

llel to red

ectroencep

matically. C

erimental p

resting ph

mental day

blood sa

nd blood s

od respec

4-h and 5-m

n stimulus.

at lights-on

assi-Zucco

back or m

t give visu

s. This me

sleep dep

ted after c

lasted 4 h

ly following

e animals

eceding th

urbed and

p deprivat

duce varia

phalogram

Concomita

procedures

hase and p

y started w

ampling sy

sampling s

ctively. The

min sleep

These we

by using

oni et al., 1

moved when

al activatio

ethod has

privation pe

ollecting th

and 5 min

g sleep de

to handlin

he experim

non-depriv

tion and th

ability amo

(EEG) p

antly, bloo

s were per

potentially

with weigh

ystem and

tarted at le

ese basel

deprivation

ere followed

the gentle

1993; Gras

never it sh

on anymor

shown to

eriod (Gras

he t= 245 m

but for sim

eprivation,

g, they we

mental da

ved in the

he stress r

ong anima

parameters

od was s

rformed du

disturbing

hing the a

d activatin

east 1 h la

ine period

n or non-d

d by a 3.5-

e handling

ssi-Zuccon

owed beha

re, the anim

effectively

ssi-Zuccon

min blood s

mplicity rea

animals w

ere handle

ay. Under

eir home c

response

57

als and

s were

sampled

ring the

g stimuli

animals,

ng their

ater with

ds were

deprived

-h post-

method

ni et al.,

avioural

mal was

y induce

ni et al.,

sample.

asons is

were left

ed for at

control

cages in

Chapte

58

Biotele

The im

depend

obtaine

Becaus

animal

values

receive

comput

blood p

seven

many a

Blood

Blood w

samplin

minimiz

were c

recove

recove

centrifu

assaye

(Mouse

Solon,

Statist

To ass

hormon

correct

used. E

er 3

emetric da

mplanted t

dent frequ

ed by coun

se the tra

were hard

were cal

ed by an a

ter using D

pressure, b

animals in

artefacts in

sampling

was sampl

ng machin

ze possibl

collected ev

ry of sleep

ry closely

uged for 5

ed in duplic

e/Rat Cort

OH, USA)

ics

sess the e

nal respon

tion epsilon

Even thoug

ata acquis

transmitter

ency mod

nting the n

nsmitter w

dly detecte

lculated fr

ntenna bo

Dataquest

body temp

n 10-s epo

n the EEG

and assa

ed using th

ne. Animal

e stress-c

very 10 –

p deprivatio

y. The sa

min at 32

cate for co

ticosterone

with a sen

effect of s

nses, a r

n (ε) for v

gh the aim

sition and

r emitted

dulated sig

number of

was implan

d by the re

rom the b

ard placed

Labpro so

erature an

chs and a

recordings

ays

he jugular

s were ha

confounding

60 min. S

on than du

amples we

210 rpm. S

orticostero

e125I RIA

nsitivity of

sleep depr

repeated

violation of

m initially w

analysis

blood pre

gnals. For

f changes

nted in th

eceiver, bu

blood pres

d under ea

oftware (Da

nd locomot

veraged a

s, these sig

vein cathe

abituated t

g effects o

Samples w

uring sleep

ere stored

Subsequen

one with a

Kit, for re

3.0 ng/ml.

rivation on

measures

f the homo

was to use

essure, bo

r gross loc

in signal

e abdome

ut horizonta

ssure regi

ach animal’

ataScience

tor activity

and stored

gnals could

eter connec

to the bloo

of it. Sma

were taken

p deprivatio

d inside t

tly, plasma

double an

esearch on

n the beh

ANOVA

ogeneity in

e a cross-o

ody tempe

comotor a

strength o

en, vertica

al changes

strations.

’s cage an

es Internat

data were

into 5-min

d not be an

cted to the

od sampli

ll sample

at higher

on to be a

the mach

a was stor

ntibody rad

nly, MP B

avioural, p

with Gre

n variance

over design

erature an

activity, da

of the tran

l changes

s were. He

All signal

nd process

tional). Hea

e sampled

n bins. Due

nalysed.

e automate

ng proced

volumes o

frequency

ble to mon

ine at 4°

red at –80

dio immun

Biomedicals

physiologic

eenhouse-G

e assumpti

n, the data

d EEG

ata was

nsmitter.

s of the

eart rate

ls were

ed by a

art rate,

from all

e to too

ed blood

dures to

of 30 µl

y during

nitor the

°C until

0°C until

noassay

s, LLC,

cal and

Geisser

on was

a of the

same a

betwee

within-s

This an

recove

perform

deprive

determ

consec

used to

betwee

correla

in the

corresp

corresp

widths

points,

using S

was ac

presen

RESUL

Dynam

sleep d

Locomo

Under

rapidly

counts/

locomo

signific

animals wa

en-subjects

subject fac

nalysis wa

ry of slee

med to det

ed and no

ine the

cutive reco

o compute

en the loco

tions, the

graphs,

ponding ti

ponding tim

depending

were used

SPSS 15.0

ccepted at

ted as mea

LTS

mics of the

deprivatio

otor activit

non-depriv

at the sta

/min (Figu

otor activity

ant time*

as not pre

s factor (tw

ctor. The

s performe

ep depriva

termine th

n-deprived

differences

very perio

e correlatio

omotor ac

mean valu

was set

ime point

me point m

g on the

d to comp

0 software

t p-values

an + SEM.

e behavio

on

ty

ved contro

art of the

ure 1 pane

y compare

*treatment

sent in bo

wo levels;

different ti

ed separat

ation perio

he specific

d control c

s betwee

d. The Pe

ons for th

ctivity, phy

ue for each

together

. Only va

measurem

parameter

ute a corre

(SPSS in

<0.05 an

.

ural, phys

l condition

light perio

el A). Dur

d to non-d

interactio

Sleep

oth groups.

control an

ime points

tely for the

od. When

time poin

conditions

n the 30

arson’s Biv

he sleep-de

ysiological

h paramete

with the

alues of

ent were

r collected

elation coe

c., Chicag

nd a trend

siological

s, locomot

od (p=0.02

ring sleep

deprived co

on, but w

p deprivat

. Therefore

nd sleep de

s were use

e sleep de

appropria

nts at whic

differed. P

0-min dar

variate cor

eprived re

and horm

er at a cert

value of

which bo

included th

d. All valu

efficient. A

o, IL, USA

d was acc

and horm

tor activity

), reaching

deprivatio

ontrol cond

with a s

tion and th

e, treatme

eprivation)

ed as with

eprivation p

ate, post-

ch the val

Paired t-te

rk, sleep

rrelation co

esponse pa

monal resp

tain time p

a differe

oth measu

herefore u

es, over t

All analyses

A). The lev

cepted at p

monal resp

levels sign

g stable v

on a signif

ditions was

ignificant

he stress r

nt was use

) rather tha

hin-subject

period and

-hoc t-test

ues under

ests were u

deprivatio

oefficient te

atterns ov

onses. Fo

point, as dis

ent param

urements

using differ

the differe

s were pe

vel of sign

p<0.10. D

ponses to

nificantly d

values arou

ficant incre

s induced,

treatment

response

59

ed as a

an as a

t factor.

for the

ts were

r sleep-

used to

on and

est was

ver time

or these

splayed

meter at

had a

rent bin

ent time

rformed

ificance

ata are

o 4 h of

declined

und 0.8

ease in

with no

t effect

Chapte

60

(F1,12=1

elevate

situatio

immed

termina

signific

circadia

for the

betwee

Heart r

Under

start of

Paired

shows

induced

signific

(F1,12=4

rate va

compa

depriva

termina

control

differen

rate va

those r

er 3

13.4, p=0.0

ed during

on but were

iately prec

ated, stable

antly belo

an resting

recovery o

en sleep-de

rate

non-depriv

f the light

t-tests co

a tendency

d a close

ant time*t

4.04, p=0.0

lues tende

rison to t

ation, lowe

ation of the

values wit

nce betwee

lues during

reached du

003) and n

the whole

e lower tha

ceding sle

e control le

ow those

phase (p=

of sleep d

eprived an

ved contro

period, rea

onfirmed th

y to decrea

to signific

treatment

06) and a s

ed to stay e

he last 30

er levels

e sleep de

thin 5 min

en the slee

g the recov

uring sleep

no significa

e period o

an levels re

eep depriv

evels were

reached b

=0.001) an

eprivation

d control c

ol conditio

aching sta

hat the he

ase after th

cant increa

interaction

significant

elevated th

0 min of

were rea

eprivation

and ANOV

ep-deprive

very of sle

p deprivatio

ant time ef

of sleep d

eached du

vation (p=0

e re-establi

before the

nd during

period con

conditions w

ns, heart

ble values

eart rate u

he lights-o

ase compa

n, but a

time effect

hroughout

the dark

ached dur

procedure

VA for the

d and non

ep depriva

on (p=0.004

ffect. Locom

deprivation

uring the la

0.005). Wh

ished with

e beginnin

sleep dep

nfirmed th

were prese

rate levels

s around 3

nder non-

n stimulus

ared to the

close to s

t (F48,576=4

the whole

phase im

ring the

, heart rat

recovery p

n-deprived

ation period

4).

motor activ

n compare

ast 30 min

hen sleep

in 5 min a

g of the

privation (p

at no sign

ent during

s gradually

61 bpm (F

-deprived c

(p=0.09).

e control c

significant

4.07, ε=0.1

sleep dep

mmediately

4-h sleep

te values r

period show

control co

d were sig

vity values

ed to the

of the dark

p deprivatio

nd reached

light phas

p=0.008). A

ificant diffe

this period

y declined

Figure 1 pa

control co

Sleep dep

condition,

treatmen

3 p=0.001

privation pe

preceding

p deprivat

returned to

wed no sig

ndition. Th

nificantly lo

s stayed

control

k phase

on was

d levels

se, i.e.,

ANOVA

erences

d.

d at the

anel B).

nditions

privation

with no

t effect

). Heart

eriod. In

g sleep

tion. At

o stable

gnificant

he heart

ower as

Blood p

Under

by the

Exposu

levels a

sleep d

the blo

those

decline

Body te

After th

reachin

compa

i.e., circ

a signif

induced

p=0.09

effect

whole 4

did no

beginn

for the

interact

signific

depriva

min. Th

below t

pressure

non-depriv

lights-on s

ure to 4-h s

and to lev

deprivation

ood pressu

reached d

ed after sle

emperature

he lights-o

ng stable

red to the

cadian res

ficant incre

d with a c

), a signif

(F48,576=8.9

4 h of slee

t exceed

ing of the

e recovery

tion (F42,50

ant time e

ation proce

he values

those reac

ved contro

stimulus an

sleep depr

vels under

n, blood pr

ure values

during slee

ep depriva

e

on stimulu

values aro

baseline p

sting phase

ease in bo

close to si

ficant trea

99, ε=0.09

ep deprivat

baseline

light phas

of sleep

04=5.49, ε=

effect (F42,5

edure, body

during thi

ched during

ol condition

nd values f

rivation did

non-depri

ressure did

for the sle

ep depriva

ation.

us, body t

ound 38 °

period, i.e.

e (p=0.03)

ody temper

gnificant t

tment effe

9, p<0.001

tion as com

values ind

e, i.e., circ

deprivatio

=0.081, p=

504=5.82, ε=

y temperat

is recovery

g the sleep

Sleep

ns, blood p

fluctuated a

d not affect

ved contro

d not diffe

eep-depriv

ation (p<0

emperatur

°C and re

30 min be

(Figure 1 p

rature as c

time*treatm

ect (F1,12=5

1). Body t

mpared to

dicating th

cadian rest

on period

=0.002), n

=0.081, p=

ture decre

y of sleep

p deprivatio

p deprivat

pressure w

around 105

t blood pre

ol conditio

er from the

ved conditi

.001) indic

re decreas

eaching sig

efore the b

panel D). D

compared

ment intera

5.05, p=0.

temperatur

the non-de

hat levels

ting phase

showed a

no significa

=0.001). Af

ased slow

deprivatio

on period (p

tion and th

was not sig

5 mmHg (F

ssure com

ns. Also d

e control a

on were s

cating tha

sed slowly

gnificantly

beginning o

During 4-h

to the con

action (F48

.04) and a

re stayed

eprived con

comparab

e, were ma

a significa

ant treatm

fter termin

ly to contro

on period

p<0.001).

he stress r

nificantly a

Figure 1 pa

mpared to b

during reco

animals. Ho

significantly

at blood p

y for the c

lower va

of the light

sleep dep

ntrol situati

8,576=2.07,

a significa

elevated

ntrol condi

ble to befo

aintained. A

nt time*tre

ent effect,

ation of th

ol levels w

were sign

response

61

affected

anel C).

baseline

overy of

owever,

y below

pressure

controls

lues as

t phase,

privation

ion was

ε=0.09,

ant time

for the

ition but

ore the

ANOVA

eatment

, and a

he sleep

within 40

ificantly

Chapte

62

Cortico

For the

slightly

around

increas

a signi

treatme

p=0.00

the dar

4-h sle

recove

showed

p=0.05

signific

minutes

min aft

corticos

sleep d

er 3

osterone

e non-dep

but signi

27 ng/ml

se in cortic

ificant tim

ent effect (

3). The lev

rk period (p

ep depriva

ry period i

d a close

2) and no

antly eleva

s later, co

er which c

sterone lev

deprivation

prived con

ficantly by

(Figure 1

osterone le

e*treatmen

(F1,12=7.48

vels were a

p<0.001). C

ation perio

mmediatel

e to signif

significant

ated for a

orticosteron

control leve

vels in the

(p=0.03).

ntrol cond

y the light

panel E).

evels comp

nt interact

8, p=0.02)

also signifi

Corticoster

d (maximu

ly following

ficant time

t sleep dep

another 15

ne levels s

els were re

e recovery

dition, plas

ts-on stim

The 4-h s

pared to th

tion (F3,36=

and a sign

icantly incr

rone was m

um averag

g sleep de

e*treatmen

privation an

5-min until

significantly

eached aga

of sleep d

sma cortic

ulus (p=0.

sleep depri

he non-dep

=3.40, ε=0

nificant tim

reased com

mostly elev

e of 76 ng

privation, t

nt interacti

nd time eff

reaching

y dropped

ain. This re

deprivation

costerone

.004) and

ivation ind

prived cont

0.82, p=0.

e effect (F

mpared to

vated at the

g/ml). Durin

the cortico

ion (F9,108

fects. Cort

control lev

below con

esulted in

period co

levels inc

levels flu

uced a sig

trol conditio

04), a sig

F3,36=6.28,

the last 30

e beginnin

ng the 3-h

osterone re

8=2.889, ε

ticosterone

vels again

ntrol levels

significant

ompared to

creased

uctuated

gnificant

on, with

gnificant

ε=0.82,

0 min of

g of the

30-min

esponse

ε=0.318,

e stayed

n. Thirty

s for 60

ly lower

o during

Cor

ticos

tero

ne (

ng/m

l)

0

20

40

60

80

100

Blo

od p

ress

ure

(mm

Hg)

95

100

105

110

115

120

Hea

rt r

ate

(bpm

)

330

360

390

420

450

Bod

y te

mpe

ratu

re (

°C)

37,0

37,5

38,0

38,5

39,0

39,5

Act

ivity

(co

unts

/min

)

0

2

4

6

8

10

12

Figure 1(panel Cconditioas 5-mincorticost(+ 5 minfor the (black), *p<0.05

-40 0

-40 0

-40 0

-40 0

A

B

C

D

E

1. Time courC), body temn (closed syn averages +terone measn) sleep dep3-h 30-min the 30-min ; (*)p<0.10.

40 80

40 80

**

40 80

40 80

((*)

*

*

rse of changperature (pambols, n=7)

+ SEM for thesurements. Tprivation or npost-sleep drise (grey) a

120 160

120 160

*

120 160

120 160

*) (*)

**

(*) (**

es in locomoanel D) and pand for the ce physiologic

The responsenon-depriveddeprivation pand light (wh

Sleep

Time (min

0 200 24

200 240

*

200 240

200 240

) *

*)(*) *

*

*

otor activity (plasma corticcontrol condical measuremes are shown control peri

period. The hite) period.

p deprivat

n)

40 280 3

0 280 3

0 280 3

0 280 3

* *

(*)*

(panel A), hecosterone (pition (open syments and fon for the last od (indicatedbars undernSignificance

tion and th

20 360 4

320 360

320 360

320 360

(*)*

C

eart rate (pananel E) for thymbols, n=7or every 10 - 30 min of thd by area be

neath the gra: sleep depr

he stress r

400 440

400 440

400 440

400 440

Control (n=7)Sleep depriva

nel B), bloodhe 4-h sleep). Data are e60 min + SE

he dark perioetween the laph indicaterivation versu

response

63

480

480

480

480

ation (n=7)

pressurep-deprivedexpressedEM for thed, the 4-hines) and the darkus control

Chapte

64

Assoc

Table

over tim

plasma

correla

p<0.00

p=0.04

with the

plasma

pressu

p<0.00

(r=0.46

with the

physiol

pattern

plasma

was fou

pressu

er 3

iations be

1 shows t

me of loco

a corticost

tion with t

1), body t

). The hea

e blood pr

a corticost

re pattern

1) pattern

6, p=0.08).

e plasma c

ogical res

were corr

a corticoste

und with th

re.

Act HR BP BT Cort

Act: lotempe(*)p<0

Tablepatter

etween the

he correla

omotor ac

terone. Th

he pattern

temperatur

art rate res

ressure (r=

terone (r=0

was sign

n and tend

. The bod

corticoster

sponse pa

related am

erone patte

he pattern

Act

1.00 0.86* 0.81* 0.81* 0.53*

ocomotor acterature; Co0.10.

1. Correlans over time

e behaviou

ation coeffi

ctivity, hea

he pattern

n of heart

re (r=0.81

sponse pa

=0.82, p<0

0.61, p=0

nificantly c

ded to be

y tempera

rone respo

tterns ove

ong each

ern, a sign

of locomo

HR

1. 000.82*0.78*0.61*

tivity; HR: hert: plasma

ation coeffic of Act, HR,

ural, phys

icient for t

rt rate, blo

n of locom

rate (r=0.8

, p<0.001)

ttern over

0.001), bod

.01) respo

correlated

correlated

ature respo

onse but w

er time an

other durin

ificant corr

otor activity

BP

1.000.78*0.46(*

eart rate; BPcorticostero

ient for theBP, BT and

siological a

the sleep-d

ood press

motor act

86, p<0.00

) and plas

time was

dy tempera

onse patte

with the

d with tha

onse was

was with al

nd the beh

ng and afte

relation co

y, heart rat

BT

1.00

*) 0.39

P: blood presone. Signifi

e sleep-deprCort (n=7).

and horm

deprived r

ure, body

tivity show

01), blood

sma cortic

also signif

ature (r=0.

erns over

body tem

at of plasm

not signif

l other res

havioural l

er sleep de

efficient fo

te and a te

Cort

1.00

ssure; BT: boicance:*p<0.

rived respon

onal resp

response p

temperatu

wed a sig

pressure (

costerone (

ficantly co

78, p<0.00

time. The

mperature (

ma cortico

ficantly co

sponses. T

locomotor

eprivation.

or the grou

endency fo

ody 05;

nse

onses

patterns

ure and

gnificant

(r=0.81,

(r=0.53,

rrelated

01) and

e blood

(r=0.78,

osterone

rrelated

Thus, all

activity

For the

p mean

or blood

DISCU

One of

multiple

sleep d

how be

gentle

increas

and a

non-de

increas

tended

increas

increas

indicati

reflects

Moreov

related

the re

vasoco

Therefo

activate

human

respect

1996; S

al., 200

catecho

compa

T

howeve

rate an

of the

below,

SSION

f the shortc

e behaviou

deprivation

ehavioural,

handling s

ses in gros

tendency

eprived co

sed at mos

to be incr

sed during

se in hea

ve of sym

s HPA ax

ver, the in

to both HP

esult of

onstriction

ore we co

ed in respo

and anim

tively durin

Suchecki e

06; Sgoifo

olamine le

red to duri

The activa

er be cons

nd body tem

light phas

normal wa

comings in

ural, physio

n within the

physiolog

sleep dep

ss locomo

for an inc

ontrol cond

st time poin

reased dur

the first h

rt rate an

mpathetic a

xis activity

ncrease in

PA axis an

e.g. incr

that can

onclude th

onse to 4-

mal studie

ng sleep d

et al., 1998

et al., 200

evels, indi

ng sleep (A

ation of the

sidered mild

mperature

se, i.e. cir

aking levels

n the prese

ological an

e same an

gical and ho

rivation. A

tor activity

rease in h

dition. Loc

nts during t

ring most t

hour of sle

nd blood p

activity, w

y (Axelrod

n body tem

nd SAM ac

reased m

be the res

hat both t

-h sleep de

es showing

eprivation,

8; Spiegel

06; Meerlo

icating SA

Akerstedt a

e SAM sys

d. Sleep d

that was o

rcadian res

s during th

Sleep

ent state o

nd hormon

nimal. The

ormonal st

Acute sleep

y, body tem

heart rate

comotor a

the sleep d

time points

eep depriv

pressure

whereas th

and Rei

mperature

ctivation. B

metabolism

sults of sy

he SAM s

eprivation.

g increase

, confirmin

et al., 199

et al., 200

AM system

and Frobe

stem and H

eprivation

observed in

sting phas

he last 30 m

p deprivat

of knowledg

nal read-ou

refore, the

tress param

p deprivat

mperature

and blood

activity an

deprivation

s, whereas

vation. The

in respons

e increase

sine, 198

levels is

Body tempe

, muscle

ympathetic

system an

This is in

ed cortisol

g HPA axi

99; Chapo

08). Other

m activatio

rg, 1979; I

HPA axis

prevented

n the contr

se. Levels

min of the

tion and th

ge in sleep

uts of stres

e present s

meters we

tion induce

and plasm

pressure

d body te

n period, a

s corticoste

e observed

se to slee

e in plasm

4; Johnso

most like

erature lev

activity

c and HPA

nd HPA a

agreemen

l and cort

is activity (

otot et al.,

studies als

on, during

rwin et al.,

in the pres

d the norma

rol situation

comparab

dark period

he stress r

p research

ss are affe

study inves

re affected

ed mild, te

ma cortico

compared

emperatur

nd also he

erone was

d tendency

ep depriva

ma cortico

on et al.,

ely also in

els will cha

and pe

A axis act

axis system

nt with mo

ticosterone

(von Treue

2001; Hip

so showed

wakefuln

, 1999).

sent study

al decline

n at the be

ble to, or

d precedin

response

65

h is how

ected by

stigated

d by 4-h

emporal

osterone

d to the

e were

eart rate

s mostly

y for an

ation is

osterone

1992).

ndirectly

ange as

eripheral

tivation.

m were

st other

e levels

er et al.,

polide et

d higher

ness as

y should

in heart

eginning

slightly

ng sleep

Chapte

66

depriva

increas

wakefu

reache

conside

1993; V

sleep d

returne

control

and pla

are in a

catecho

(Axelro

corticos

HPA ax

et al.,

change

vasoco

T

proced

this wa

corticos

Moreov

inactive

measu

this ind

affected

automa

conditio

physiol

A

that m

discuss

er 3

ation were

se in hear

ulness (Toc

d higher le

ered low a

Van den B

deprivation

ed to contr

values up

asma corti

agreement

olamines,

od and R

sterone se

xis and is

1992). Als

e due to

onstriction.

The prese

ures. The

as achieved

sterone va

ver, the lo

e during

rements w

dicates th

d by the s

atical mea

ons, indee

ogical and

A point of

ediates th

sion is whe

maintaine

rt rate and

chikubo et

evels than

as they we

Buuse et a

n procedur

rol values w

pon termina

icosterone

t with the k

which in tu

Reisine, 19

ecretion is a

therefore

so, body te

o change

ent study a

measurem

d. Normal

alues were

ow locomo

most of t

were taken

hat the an

sampling p

asurement

d allowed

d hormonal

discussion

he adverse

ether stres

ed. This is

d blood pr

al., 1996;

n during re

ere below

al., 2001; S

re, the res

within 40 m

ation of the

showed a

knowledge

urn have i

984; John

a final resu

not a fast

emperature

es in m

also reduc

ments und

and stable

e maintain

otor activity

the obser

during the

nimals und

procedures

ts under

high qualit

l stress pa

n is to what

e consequ

s system a

s in accord

ressure to

Sforza et a

elaxed wak

levels see

Suchecki e

sponses s

min. Wher

e sleep dep

a slower d

that SAM

mmediate

nson et a

ult of a neu

response

e response

metabolism,

ced stress-

er non-de

e physiolog

ned throug

y levels in

rvation pe

e light pha

der non-de

s which c

controlled

ty un-confo

rameters in

t degree s

uences of

activation i

dance with

owards lev

al., 2004).

kefulness b

en during m

et al., 200

showed dif

reas heart

privation p

decline. Th

activation

effects on

al., 1992)

uroendocrin

(Axelrod a

es are in g

, muscle

-confoundi

prived con

gical value

ghout the

ndicate tha

riod. This

ase, i.e. the

eprived co

onfirms th

d, home

ounded me

n parallel.

leep depriv

sleep de

in respons

h other stu

vels reache

Only plasm

but these

mild stress

2). Upon t

fferent time

rate had a

rocedure,

hese differ

results in

n the cardi

and the

ne cascad

and Reisin

general de

activity

ing effects

ntrol condit

es togethe

entire ob

at the cont

was exp

e resting p

ontrol con

hat the use

cage and

easuremen

vation con

eprivation.

e to sleep

udies show

ed during

ma cortico

levels can

s (Buwalda

termination

e courses

a rapid de

body temp

rent time p

a rapid rel

ovascular

knowledg

e activated

e, 1984; J

elayed as

and pe

s of the sa

tions confi

r with low

bservation

trol anima

pected sin

phase. Alto

nditions we

ed approa

d freely

nts of beha

stitutes a s

Another p

deprivatio

wing an

normal

osterone

still be

a et al.,

n of the

but all

ecline to

perature

patterns

lease of

system

ge that

d by the

Johnson

this will

eripheral

ampling

irm that

plasma

period.

ls were

nce the

ogether,

ere not

ach with

moving

avioural,

stressor

point of

on is the

result o

depriva

activati

hypothe

increas

wakefu

corticos

during

during

2002).

with b

depriva

stressfu

activate

et al.,

within t

that the

correla

a cons

depriva

behavio

proced

depriva

wakefu

Koolha

with th

constitu

showed

similar

degree

O

activity

activati

of sleep lo

ation proce

on is due

esized tha

se the act

ulness (Me

sterone re

the first ho

mild stress

We believ

ehaviour

ation. The

ul situation

ed in any c

2003). An

their cages

e locomoto

ted with th

siderable p

ation is a

oural activ

ure. This

ation may

ulness ass

aas and co

he behavi

ute a stres

d that the

response

e correlated

Overall, w

of the ne

on was clo

ss per se

edure. Also

e to phys

at in orde

tivity of th

eerlo et a

eached hig

our of slee

s (Buwalda

ve that the

may facili

classical

ns, but are

condition t

imals wer

s, which ind

or activity p

he patterns

part of the

direct refle

vity that w

supports t

have be

sociated w

o-workers,

oural resp

ssor (Koolh

different

pattern ov

d with the H

we conclud

uroendocr

osely relat

or a cons

o, one sho

ical activit

er to cons

he stress

al., 2008)

gher level

p deprivat

a et al., 19

analysis o

itate the

stress sy

e also cruc

that require

e forced t

duced mild

pattern dur

s of the ph

e classical

ection of t

was induc

the idea t

een neces

with sleep

this assoc

ponse als

haas et al

read-outs

er time wh

HPA axis r

de that sh

rine and ph

ed to the p

Sleep

equence o

ould determ

ty induced

sider sleep

systems

. As our

ls than du

ion, but the

993; Van de

of the activ

interpretat

ystems are

cial for mo

es or caus

to be awak

d physical a

ring and af

ysiologica

stress sys

the metabo

ced by ou

hat mild s

ssary to

deprivatio

ciation of t

so indicate

., 2011). T

indicative

hereas the

response.

hort sleep

hysiologica

physical ac

p deprivat

of the stres

mine to wh

d to keep

p deprivat

beyond t

combined

uring relax

ese levels

en Buuse e

vation of th

tion of th

e not only

bilization o

ses behavi

ke by stro

activity. Co

fter sleep d

l and horm

stem activ

olic require

ur gentle

stress syst

support t

on. In line

the physio

es that s

The correla

of sympa

sympathet

deprivatio

al stress s

ctivity disp

tion and th

ssfulness o

hat extent t

the anim

tion as st

those see

d measure

xed wakef

were still

et al., 200

he stress s

e conseq

y activated

of energy

ioural activ

oking them

orrelationa

deprivation

monal resp

vation in re

ements fo

handling s

tem activa

he increa

with the

ological/hor

sleep depr

ational ana

athetic acti

tic respons

on mildly

ystems. T

layed by th

he stress r

of the use

the stress

mals awak

ressful, it

n during

es showe

fulness an

below thos

1; Sucheck

ystems in

uences o

d in respo

and are th

vation (Lea

m or movin

l analysis s

n was sign

onses. The

esponse t

r normal o

sleep dep

ation during

sed activ

stress th

rmonal res

rivation m

alysis furth

ivity had a

se was to a

affects the

his stress

he animals

response

67

ed sleep

system

ke. It is

should

relaxed

d, only

nd only

se seen

ki et al.,

concert

f sleep

onse to

herefore

al-Cerro

ng them

showed

ificantly

erefore,

o sleep

ongoing

privation

g sleep

ity and

eory of

sponses

may not

hermore

a highly

a lesser

e basal

system

s during

Chapte

68

the sle

handlin

betwee

and sin

sleep d

impact

ACKNO

The au

den Kie

er 3

eep depriv

ng procedu

en the phy

nce all me

deprivation

on the ani

OWLEDGE

thors woul

eboom for

vation sess

ure in ord

ysiological/

easuremen

n per se, a

imal.

EMENTS

ld like to th

their techn

sion. This

der to pro

/hormonal

nts stayed

as induced

hank Leen

nical assist

physical

voke wake

and beha

within the

by our ge

Raeymaek

tance.

activity w

efulness.

avioural ac

normal ra

entle handl

kers, Annic

was induce

Since a c

ctivity respo

ange, we c

ling proced

ck Heylen

ed by our

close disso

onse was

conclude t

dure, has

and Gerd

gentle-

ociation

visible,

that 4-h

a minor

van

Chapter 4

Short sleep deprivation by gentle handling is a mild activator of the stress systems but does not affect the

subsequent response to novelty exposure

W. Beerling1, 2, J.M. Koolhaas2, A. Ahnaou1, P. Meerlo2 and

W.H.I.M. Drinkenburg1

1 Department of Neuroscience, Janssen Research & Development, a division of

Janssen Pharmaceutica N.V., Turnhoutseweg 30, 2340 Beerse, Belgium; 2 Department of Behavioural Physiology, University of Groningen, Nijenborgh 7, 9747 AG

Groningen, The Netherlands

Chapte

70

ABSTR

Sleep d

affect th

acute s

novelty

and the

explorat

deprivat

distribut

method

total sle

placing

undistur

continuo

tempera

Rapid E

togethe

deprivat

novelty

a conco

significa

sleep de

during t

increase

affecting

deprivat

body te

sleep. P

respons

h of slee

and to c

sleep d

conclud

physiolo

termina

er 4

RACT

deprivation d

he reactivity

sleep depriv

exposure.

e physiolog

tive behav

tion affects

tion with NR

. To study

eep depriva

the rat in

rbed. A set-

ous monito

ature and p

Eye Movem

r with a

tion followe

phase. Sle

omitant incre

ant increase

eprivation p

the post-no

e in locom

g plasma

tion termina

emperature

Prior sleep

ses after no

ep deprivat

cause effec

deprivation

de that acut

ogical stres

tion.

does not on

y of these s

vation affec

Novelty exp

ical and ho

vioural activ

s physiolog

REM delta

this, adult

ation by gen

n a clean,

-up combin

oring of g

plasma cort

ent (NREM

permanent

ed by a rec

ep deprivat

ease in time

e in delta p

procedure. T

ovelty expos

motor activit

corticostero

ation, induc

and plasm

p deprivatio

ovelty expos

ion by our g

cts that are

is a mild

te sleep de

s response

nly affect th

ystems to c

cts the beh

posure is kn

ormonal res

vity. We a

ical, hormo

power to fu

male Sprag

ntle handlin

empty ca

ing radiotel

gross locom

ticosterone

) delta pow

t heart ca

covery peri

tion was ass

e spent awa

power during

The increas

sure phase

ty, heart ra

one levels.

ed an incre

ma corticost

on did not

sure was un

gentle hand

still detecta

activator o

eprivation d

e to novelty

he basal ac

challenges.

havioural, p

nown to ind

sponses ar

also analys

onal and lo

urther valida

gue-Dawley

ng and subs

age. Under

emetry and

motor activ

levels as w

wer. To do s

atheter. Me

iod with su

sociated wit

ake. A tend

g NREM sl

sed delta po

e. Sleep de

ate, blood p

Exposure

ease in loco

erone with

affect thes

naffected by

dling proced

able after n

of the auto

does not aff

exposure a

ctivity of the

Therefore,

hysiologica

duce mild ac

re closely re

sed how a

ocomotor a

ate the gen

y rats were

sequently to

r control c

d automated

vity, heart

well as slee

o, rats were

easurement

ubsequent n

th a near co

dency for a

eep was pr

ower during

eprivation a

pressure a

to novelty

omotor activ

a concomi

se response

y prior slee

dure is suffic

novelty expo

onomic stre

fect the sub

as measure

e stress sys

this study a

al and horm

ctivation of

elated to th

acute gent

activity leve

ntle handlin

exposed to

o 15-min n

conditions,

d blood sam

rate, bloo

ep-wake dis

e implanted

ts were ta

novelty exp

omplete red

rebound in

resent upon

g NREM sle

lso caused

nd body te

y, starting

vity, heart ra

itant lack o

es. Also th

ep deprivatio

cient to dep

osure. More

ess system

bsequent n

ed 1.5 h afte

stems but m

aimed to sh

monal respo

the stress

he ongoing

tle handlin

els and slee

g sleep dep

o either 4 o

ovelty expo

animals w

mpling was

od pressure

stribution a

d a small tra

aken during

posure and

duction of sl

NREM slee

n terminatio

ep was still

d a mild, te

emperature

1.5 h afte

ate, blood p

of NREM an

he recovery

on. In concl

prive rats fro

eover, 4 an

s. We furt

neuroendocr

er sleep dep

may also

how how

onses to

systems

, mainly

g sleep

ep-wake

privation

or 6 h of

osure by

were left

used for

e, body

nd Non-

ansmitter

g sleep

a post-

leep and

ep and a

on of the

present

mporary

without

er sleep

pressure,

nd REM

y of the

lusion, 6

om sleep

nd 6 h of

hermore

rine and

privation

INTRO

The ex

depriva

Huffcut

hypothe

adverse

the ne

adreno

are the

results

bloodst

axis res

subseq

corticos

behavio

as met

Reisine

2008).

report m

to slee

et al., 1

al., 200

sugges

regulat

stress-

et al., 2

S

but ma

studies

affect t

depriva

(repeat

ODUCTION

xact functio

ation is de

tt, 1996). T

eses have

e consequ

euroendoc

omedullary

e two most

in the rel

tream (Axe

sults in the

quently stim

sterone in

oural, emo

abolic func

e, 1984; Jo

As review

mild activa

p deprivati

1998; Irwin

06; Sgoifo

sts that c

ion of thes

related dis

2005; Nova

Sleep dep

ay also affe

s suggest t

the HPA a

ation (i.e.

ted 20 h s

N

on of sleep

etrimental

The under

e been form

uences of

rine stres

(SAM) sy

t importan

lease of th

elrod and R

e release o

mulates th

rodents fr

otional, cog

ctions to e

ohnson et

wed by Mee

ation of the

ion (Akerst

n et al., 19

o et al., 2

hronic or

se stress s

sorders suc

ati et al., 20

rivation m

ect the rea

that acute s

axis respo

48 h of

sleep dep

p is still un

to good h

lying mech

mulated. O

sleep dep

ss system

ystem and

t neuroend

he catech

Reisine, 19

of the pituit

he release

rom the ad

gnitive, ph

nable the

al., 1992;

erlo and co

e stress sys

tedt and F

99; Spiege

2006; Mee

frequent

systems, w

ch as depr

008).

ay not onl

activity of t

sleep depr

onse to a

total slee

rivation pe

Sle

nknown, ye

health (Fo

hanisms a

One of the

privation ar

ms (Meerlo

d the hypo

docrine str

olamines

984; Johns

tary adren

e of the g

drenal glan

hysiologica

individual t

; Buckley

o-workers,

stems, in p

Froberg, 19

el et al., 19

erlo et al.,

restriction

which may

ression (Bu

y affect th

these syst

rivation (20

subsequen

p depriva

er day) al

eep depriva

et it is com

rd and Ka

re still poo

e hypothes

re mediate

o et al.,

othalamic-p

ress syste

adrenaline

son et al., 1

ocorticotro

lucocortico

nd. These

l, hormona

to deal wit

and Schat

controlled

particular o

979; von T

999; Chapo

2008). M

n of sleep

y contribute

uckley and

e basal ac

tems to ch

0 h of total

nt stresso

tion) or 8

ters the H

ation and

mmon know

amerow, 1

orly unders

ses states

ed by chan

2008). T

pituitary-ad

ms. SAM

e and nora

1992). Acti

opic hormo

oid cortiso

hormones

al, brain fu

th the situa

tzberg, 20

d human a

of the HPA

reuer et al

otot et al.,

Moreover,

p may gr

e to the sy

d Schatzbe

ctivity of th

hallenges.

sleep dep

r whereas

8 days of

HPA axis

d novelty ex

wledge tha

989; Pilch

stood, but

that some

nges in ac

The symp

drenal (HP

system ac

adrenalin i

ivation of t

one (ACTH

ol in huma

s in turn in

unctioning

ation (Axel

05; Meerlo

and rodent

A axis, in re

l., 1996; S

2001; Hip

existing lit

radually al

ymptomato

erg, 2005;

he stress s

Controlled

privation) d

s prolonged

sleep res

response

xposure

71

at sleep

her and

several

e of the

ctivity of

pathico-

PA) axis

ctivation

into the

he HPA

H) which

ans and

nfluence

as well

rod and

o et al.,

studies

esponse

uchecki

polide et

terature

lter the

ology of

Roman

systems

d rodent

does not

d sleep

striction

to brief

Chapte

72

restrain

2006; N

adrena

adrena

by prol

Suchec

showed

corticos

This m

Altoget

depriva

been d

depriva

T

affects

affects

subseq

by a br

Four to

sleepin

A 1.5-h

stress s

et al., 2

researc

(Ader a

1986).

activati

hormon

behavio

stress-c

depriva

mild ac

al., 20

er 4

nt or inesc

Novati et

al corticoste

al sensitivity

longed sle

cki and co-

d that sub

sterone lev

may again

ther, only a

ation or sle

done. The

ation affect

The aim o

behaviour

the subs

quent studi

rief recove

o six hou

ness for up

h recovery

systems w

2002). Nov

ch and is c

and Friedm

In an ea

on of the

nal respo

oural activ

confoundin

ation meth

ctivation of

06; Van

capable foo

al., 2008).

erone resp

y to ACTH

eep curtailm

-workers s

bsequent e

vels despi

suggest

a few contr

eep restric

erefore, th

ts the activ

of the pre

ral, physiol

sequent re

ies, rats w

ery of slee

rs of slee

p to 3 h afte

y period aft

were back t

vel cage e

considered

man, 1968

arlier study

e stress sy

nses are

vity (Beerli

ng factors

od. This m

f the stress

der Borgh

ot shock s

. Particula

ponse rem

H. Also the

ment (Sgo

subjected r

exposure t

te an una

hypersen

rolled rat s

ction and h

he presen

vated stres

esent study

logical and

eactivity to

were expos

p deprivat

ep depriva

er terminat

fter sleep d

o control le

exposure h

a mild psy

8; Hennes

y we repo

ystems an

closely

ng et al.,

as much

method eff

s systems

ht et al.,

stress in ra

rly, the AC

mained una

cardiac a

oifo et al.,

rats to 96 h

to a mild

ltered ACT

sitivity of

studies tha

hormonal r

nt state o

s response

y was to

d hormona

o novelty

sed to eithe

tion and su

ation in ra

tion of slee

deprivation

evels befo

has a long

ychologica

ssy et al.,

orted that

nd that th

related to

2011) (Ch

as possib

fectively re

(Grassi-Z

2006; Ha

ats (Meerlo

CTH respo

affected, pe

utonomic s

2006). Fu

h of parado

stressor w

TH respon

the adren

at largely fo

read-outs o

of knowled

e is limited

assess ho

l measures

exposure.

er 4 or 6-h

ubsequent

ats leads

ep deprivat

n was inclu

re exposur

history in

al stressor w

1979; Pfi

novel ca

he novelty-

o the on

hapter 2).

ble by usin

educes sle

ucconi et a

gewoud e

o et al., 20

onse was

erhaps ind

stress reac

rthermore,

oxical slee

was assoc

nse (Suche

nal gland

ocussed on

of HPA ax

dge on h

d.

ow short

s and how

For this

h sleep de

t exposure

to signific

tion (McKe

uded to m

re to the no

experime

with good

ister, 1979

ge exposu

-induced p

ngoing, m

The prese

ng a gent

eep time a

al., 1993;

et al., 201

002; Sgoifo

reduced; y

dicating inc

ctivity was

in anothe

ep deprivat

ciated with

ecki et al.,

to ACTH

n prolonge

xis reactivi

how acute

sleep dep

sleep dep

purpose,

eprivation f

e to a nove

cant increa

enna et al.

ake sure t

ovel cage

ntal roden

ecological

9; Armario

ure induce

physiologic

mainly exp

ent study r

le handling

nd causes

Grassi-Zuc

10). Furthe

o et al.,

yet, the

creased

altered

er study

tion and

h higher

, 2002).

H input.

ed sleep

ty have

e sleep

privation

privation

in two

followed

el cage.

ases in

, 2008).

that the

(Meerlo

t stress

validity

o et al.,

es mild

cal and

plorative

reduced

g sleep

s only a

cconi et

ermore,

radiote

al., 200

system

2005) w

stress p

Physio

(cortico

respon

change

electro

(NREM

depriva

taken i

depriva

allowin

primary

reactivi

acute s

METHO

Anima

In a se

Horst,

(Harlan

of surg

describ

to surg

enrichm

position

up (Da

samplin

lemetry (G

07; Tang

m (Steffens

was used,

parameter

logical (h

osterone) s

se to slee

es in

myographi

M) delta p

ation proce

n one exp

ation were

g for a com

y goal of t

ity of the

sleep depri

ODS

ls, housin

eries of 2 e

The Nethe

n, Horst, Th

gery, as su

bed in Cha

gery in p

ment and s

ned in the

ataScience

ng system

Guiol et al.,

et al., 20

, 1969; Th

which allo

s in freely

heart rate,

stress para

ep depriva

sleep-wa

ic EMG),

power we

edure. Tec

periment, t

e done. So

mparison b

he presen

neuroendo

ivation in a

ng and exp

experimen

erlands) fo

he Netherl

ubjects. Fo

apter 3. All

polycarbon

standard r

experimen

es Interna

(AccuSam

1992; Van

007) in co

hrivikraman

owed frequ

moving ra

, blood p

ameters, in

ation and

ake dis

locomotor

re determ

chnologica

therefore t

ome of th

between th

t study wa

ocrine and

a non-confo

perimenta

nts, we use

or experim

ands) for e

r experime

rats were

nate cage

rat chow a

ntal set-up

ational, St.

mpler Micro

Sle

n den Buus

ombination

n et al., 20

uent and s

ts under co

pressure,

ndicative of

novelty ex

stribution

activity le

mined to

al reasons

two experi

he measur

he effects o

as to deter

d physiolog

ounded wa

al set-up

ed 18 adu

ment 1 and

experimen

ent 1, the s

individual

s (43x27x

and water

p. This set-

. Paul, M

o, DiLab, L

eep depriva

se, 1994; L

with an

002; Royo

simultaneo

ontrolled, n

body tem

f sympathe

xposure w

(electro

evels and

validate t

s prevente

ments usi

res in bot

of 4 and 6

rmine how

gical stres

ay.

lt male Sp

d 23 adult

t 2, all wei

same rats

ly housed

x39 cm)

ad libitum

-up consis

MN, USA)

Lund, Swed

ation and

Leon et al.

automated

et al., 200

us measur

non-confou

mperature

etic and HP

were meas

oencephalo

Non-Rapid

the gentle

d all mea

ng either 4

th studies

h of sleep

w both the

ss systems

prague-Daw

male Spra

ghing 310

were used

for at leas

containing

m. The hom

sted of a ra

and an

den). With

d novelty ex

, 2004; Gr

d blood sa

04; Abelso

rement of

unding con

) and ho

PA axis ac

ured. In a

ographic

d Eye Mo

e handling

asurements

4 or 6 h o

were the

p deprivatio

basal activ

s are affec

wley rats (

ague-Daw

-330 g at t

d as for th

st two wee

g bedding

me cage co

adioteleme

automated

h 8 set-ups

xposure

73

reene et

ampling

n et al.,

multiple

nditions.

ormonal

ctivity, in

addition,

EEG,

ovement

g sleep

s to be

of sleep

e same,

on. The

vity and

cted by

(Harlan,

ley rats

the time

he study

eks prior

g, cage

ould be

etry set-

d blood

s, not all

Chapte

74

animals

surgery

for at l

were h

temper

light/da

ethical

Surger

Surgery

Piritram

subcuta

locomo

(TL11M

attache

blood

Further

subcuta

3 mm

anchor

experim

activity

Interna

The oth

trapezi

receive

al., 200

through

right at

attache

connec

or to th

er 4

s could be

y, repeated

east 24 h

handled d

rature (21

ark regime

committee

ry

y was pe

mide (dipid

aneously a

otor activity

M2-C50-PX

ed to the

pressure

rmore, two

aneously t

on either

red to the

ment 2, a

, body te

ational). Th

her two le

us) for EM

ed a jugula

02). The

h the right

trium. The

ed to the

cted throug

he automat

e housed

dly placed

in the set

daily for w

± 1°C), c

using a 30

e approved

erformed

dolor, 0.02

at start of

y, heart ra

XT, DataSc

abdominal

catheter o

o biopote

o the skull

side late

e skull wit

transmitte

emperatur

he leads fo

ads were

MG registr

ar vein cath

catheter (

jugular ve

catheter w

skin in th

gh a spiral

ted blood-s

in this set

within the

t-up prior t

weighing

controlled

0-min dim/

d all experi

under O2

25 mg/kg,

surgery. F

ate, blood

ciences Int

l wall to e

of the tra

ntial lead

and the b

eral to the

h screws

er was im

e, EEG

or EEG re

bilaterally

ration. In

heter for bl

(polyuretha

ein with the

was led su

he dorsal

to the sw

sampling m

t-up simult

eir home c

to the exp

purposes.

humidity

rise period

mental pro

2-N2O-isof

0.1 ml/10

For experim

pressure,

ternationa

ensure sta

nsmitter w

s for cort

are ends w

midline a

and dent

mplanted fo

and EMG

egistration

attached

addition, a

lood samp

ane; ID: 0

e tip of the

bcutaneou

region of

ivel and co

machine. A

taneously.

cages in th

erimental

The roo

(50 ± 10%

d with lights

otocols.

lurane an

00 g body

ment 1, a

body tem

l) was imp

abilization

was guide

tical EEG

were place

and 6 mm

tal cement

or measur

G (TL11M

were impl

to the dee

animals of

ling (Stef

0.36, OD:

catheter r

usly throug

f the neck

onnected e

After surge

Rats wer

his set-up

day. After

om was k

%) and a

s on at 06.

naesthesia

y weight) w

transmitte

mperature

planted intr

(Greene e

ed into the

G measure

ed in contac

m posterio

t (Tang e

rement of

M2-F20-EET

lanted as

eper neck

f both exp

ffens, 1969

0.84, DiL

reaching th

gh a Dacro

k. The Da

either to th

ery, animals

re therefor

and were

r surgery, a

kept at c

fixed 12

.00 a.m. Th

. The an

was admin

er to recor

and cortic

raperitonea

et al., 200

e femoral

ements we

ct with the

r to bregm

et al., 200

gross loc

T, DataS

described

muscles (

periment 1

9; Thrivikra

ab) was i

he entranc

on button th

acron butto

he infusion

s were con

re, after

housed

animals

constant

: 12 h

he local

nalgesic

nistered

d gross

cal EEG

ally and

7). The

artery.

ere led

dura at

ma and

07). For

comotor

ciences

above.

cervical

and 2

aman et

nserted

e of the

hat was

on was

pumps

nnected

to a co

cathete

for at le

Experi

After re

of anim

the sam

its effe

and pl

depriva

sleep-w

F

had co

either n

conditio

depriva

William

were s

due to

and the

n=8 for

exposu

sleep d

variabil

measu

automa

testing

of all te

F

animals

divided

ntinuous in

er) to ensu

east two w

mental de

ecovery fro

mals. The m

me. Experi

cts on gro

asma cor

ation perio

wake distrib

For experi

mpleted th

non-depriv

ons with no

ation with n

ms design w

upposed t

blood clott

erefore the

r the contro

ure conditio

deprivation

lity among

red contin

atically and

as describ

esting days

For experi

s could be

d into two g

nfusion of

ure the cat

eeks befor

esign

om surgery

methods an

iment 1 inc

oss locomo

ticosterone

od and its

bution, NR

ment 1, in

he experim

ed control

ovelty expo

novelty ex

with 3-5 d

o be expo

ting in the

e same an

ol condition

on, n=6 fo

with nove

animals a

nuously a

d repeated

bed in chap

s was take

iment 2, in

e tested si

groups of

saline + he

theter to st

re start of t

y, two expe

nd experim

cludes a 4

otor activity

e. Experim

effects o

REM delta p

total 12 an

ment as de

conditions

osure, slee

xposure. Th

ays in bet

osed to all

catheters,

nimals wer

n without n

or sleep de

elty exposu

and behav

and autom

dly. Statistic

pter 3 or si

n together

n total 16

multaneou

n=8 that h

Sle

eparin (10

tay open.

the experim

eriments w

mental des

4-h gentle h

y, heart ra

ment 2 inc

on gross lo

power and

nimals sur

scribed in

s without n

ep depriva

his was do

tween ses

conditions

some rats

re not alw

novelty exp

eprivation w

ure. Eight s

vioural, phy

matically. C

cal analysi

ignificant e

.

animals s

usly in the

had their e

eep depriva

IU/ml; 0.1

The anima

ments.

were perfor

ign used in

handling s

te, blood p

cludes a

ocomotor

d plasma co

rvived the s

chapter 3

novelty exp

tion withou

one using

sions. Usi

s with 3-5

s did not ex

ays prese

posure, n=6

without no

set-ups we

ysiological

Concomita

is showed

effect of tes

survived s

operant b

experiment

ation and

2 ml/h eac

als were a

rmed with

n these stu

sleep depri

pressure, b

6-h gentle

activity, b

orticostero

surgery. A

, the rats w

posure, non

ut novelty e

a balance

ng this de

days in be

xperience

nt in all g

6 for the co

ovelty expo

re used in

and EEG

antly, bloo

no signific

sting day, t

urgery. Be

boxes, the

tal day on

d novelty ex

ch side of t

allowed to

2 different

udies were

vation per

body temp

e handling

ody tempe

one.

After some

were subje

n-deprived

exposure o

ed and cro

esign, the a

etween. Ho

all four co

roups resu

ontrol with

osure and

parallel to

paramete

od was s

cant effect

therefore t

ecause on

16 anima

a different

xposure

75

the dual

recover

t groups

e largely

riod and

perature

g sleep

erature,

of them

ected to

d control

or sleep

oss-over

animals

owever,

nditions

ulting in

novelty

n=8 for

o reduce

rs were

sampled

of prior

the data

ly eight

als were

t day in

Chapte

76

the sam

expose

novelty

with 7 d

depriva

novelty

design

variabil

measu

automa

induced

possibi

of REM

fragme

numbe

telemet

conditio

control

locomo

n=6 an

The ex

the ligh

weighin

activati

samplin

was fo

depriva

all star

depriva

novelty

post-no

er 4

me week u

ed to sleep

y exposure

days in be

ation, slee

y exposure

with 7 day

lity among

red contin

atically and

d 8 times

lity. The pu

M sleep. S

entation pro

r of subjec

try signals

on without

condition

otor activity

d n=5 resp

xperimenta

ht phase, i

ng the anim

ng their t

ng started

ollowed by

ation (expe

rting at ligh

ation recov

y exposure

ovelty phas

sing a stan

p deprivatio

e. This was

tween ses

ep fragmen

e. This wa

ys in betwe

animals a

nuously a

d repeated

s per hou

urpose wa

Since sleep

otocol and

cts could n

and/or blo

t novelty,

with nove

y, physiolo

pectively fo

al sleep de

i.e. the cir

mals, conn

transmitter

simultane

y either a

eriment 2)

hts-on. The

very phase

e or non-no

se.

ndard circa

on, sleep f

s done us

ssions. The

ntation an

as also do

een sessio

and behav

and autom

ly. During

r, with 1.

as to reduce

p fragmen

d outcome

not be ana

ocked bloo

n=5 for s

elty and n

ogical and

or the sleep

eprivation a

rcadian res

necting the

rs. At leas

eously for

4-h slee

period, or

ese were

, based on

ovelty cont

adian time

fragmentat

ing a bala

e animals o

d control

one using

ns. Eight s

vioural, phy

matically. C

sleep frag

5 min of

e NREM s

tation was

es will not

alysed furt

od samplin

sleep depr

n=5 for sle

corticoster

p-wake res

and expos

sting phas

em to the a

st 1 h lat

a 15-min

ep depriva

in either c

followed fo

n unpublish

trol conditi

window. T

tion and co

anced and

of group 2

conditions

a balance

set-ups we

ysiological

Concomita

gmentation

interruptio

sleep episo

s not succ

be furthe

ther due to

g. This res

rivation w

eep depriv

rone meas

sponses an

ure to nov

e. The ex

automated

ter, teleme

baseline p

tion (expe

case by a n

or both stu

hed pilot da

on. These

The animal

ontrol cond

cross-ove

were also

s but were

ed and cro

re used in

and EEG

antly, bloo

, interrupti

on and 6

ode duratio

cessfully in

r describe

o insufficie

sulted in: n

ithout nov

vation with

surements,

nd NREM

velty were

perimenta

blood sam

etric recor

period. Thi

eriment 1)

non-depriv

udies by a

ata, and su

e were follo

ls of group

ditions, all

er Williams

exposed t

e all expo

oss-over W

parallel to

paramete

od was s

ons in slee

min of s

on and the

nduced, th

ed. The da

ent quality

n=4 for the

velty, n=5

h novelty,

and in n=

delta powe

performed

l day start

mpling syst

rdings and

s baseline

) or a 6-h

ved control

a 1.5-h pos

ubsequent

owed by a

p 1 were

without

s design

to sleep

osed to

Williams

o reduce

rs were

sampled

ep were

sleeping

amount

e sleep

ata of a

of their

e control

for the

for the

=7, n=8,

er.

d during

ted with

tem and

d blood

e period

h sleep

period,

st-sleep

t 15-min

75-min

Sleep d

Sleep d

to publ

short, w

back o

was lift

induce

et al., 1

t= 245

but for

depriva

sleep d

followin

caused

the two

studies

same e

Novelt

Exposu

Boer et

min to

clean,

therefo

cage e

their h

undistu

deprivatio

deprivation

lished met

whenever

r gently m

ted from it

wakefulne

1993). For

min blood

r simplicity

ation was t

deprivation

ng sleep d

d by the sle

o days pr

s, animals

experiment

y exposur

ure to nove

t al., 1990b

gently pick

empty ca

ore include

exposure. A

home cag

urbed in the

on

n started a

thods (Gra

the anima

moved. Wh

ts cage fo

ess for at l

r experime

d sample. T

y reasons

terminated

n last 6 h a

eprivation,

eep depriva

eceding th

were left u

tal room.

re

elty was pe

b; Beerling

k up the ra

age otherw

ed entering

After collec

ges. Unde

eir home c

at lights-on

assi-Zucco

l showed b

en this did

or a few s

least 80%

nt 1, sleep

Therefore,

is further

after colle

and 5 min,

, animals w

ation meth

he experim

undisturbe

erformed a

g et al., 201

at from its

wise comp

g the expe

cting the t

er non-no

cages while

Sle

using the

ni et al., 1

behavioura

d not resu

econds. T

of the slee

p deprivatio

sleep dep

r referred

ecting the t

, which is f

were left u

hod, anima

mental day

ed and non

according t

11). The ex

home cag

parable to

erimental ro

t = 15 min

ovelty con

e remaining

eep depriva

e gentle ha

1993; Gras

al signs of

lt in visua

This metho

ep depriva

on was ter

privation ac

to as 4 h

t= 365 min

further des

undisturbed

als were ha

y. For the

n-deprived

to the prot

xperimente

ge at t = -1

o its home

oom, brief

blood sam

ntrol cond

g in the sa

ation and

andling pro

ssi-Zuccon

sleep, it w

l activation

od has sho

ation period

rminated a

ctually last

h. For exp

n blood sam

scribed as

d. In order

andled for a

control p

in their ho

tocol previo

er entered

1 min and

e cage. N

f handling

mple, rats

ditions, an

ame experi

d novelty ex

ocedure ac

ni et al., 20

was stroke

n of the an

own to eff

d (Grassi-Z

after collec

ted 4 h an

periment 2

mple, whic

6 h. Imme

r to reduce

at least 10

procedure

ome cages

ously repo

the room a

place it in

Novelty ex

and force

were retu

nimals we

mental roo

xposure

77

ccording

006). In

d on its

nimal, it

fectively

Zucconi

cting the

d 5 min

2, sleep

ch made

ediately

e stress

0 min on

in both

s in the

orted(De

at t = -2

a new,

xposure

d novel

urned to

ere left

om.

Chapte

78

Biotele

Using

Interna

telemet

EMG a

signals

resulted

from th

board

using D

locomo

averag

were i

vigilanc

spectru

sleep w

predom

of body

regular

lower

Wakefu

tone, a

state w

range o

of 0.25

power

phase

experim

er 4

emetric da

the implan

ational) be

trically mo

and EEG d

s were obt

d from hor

he blood p

placed un

Dataquest

otor activity

ed and sto

mported i

ce states w

um for eac

was score

minant EEG

y moveme

r low ampli

frequencie

ulness was

and freque

was calcula

of 0.5-4 Hz

Hz for 4 s

(0-40 Hz)

and the 7

ment 1, the

ata acquis

nted trans

ehavioural

nitored. Th

ependent f

tained by

rizontal mo

pressure r

derneath e

Labpro so

y data were

ored into 5

nto Neuro

were deter

ch epoch w

ed based

G power in

ent. Rapid

tude EEG

es and ge

s scored b

ent body m

ated in 15

z was analy

s NREM sl

). This wa

75-min pos

ese were n

sition and

mitter and

, physiolo

he transmi

frequency

monitoring

ovement of

registration

each anim

oftware. He

e sampled

5-min bins.

oScore Ve

rmined off

was used

on the p

n the delta

Eye Move

with a dom

eneral lac

based on ir

movements

-min block

ysed by Fa

eep epoch

as analyse

st-novelty p

ot further a

analysis

d the Data

ogical an

tters emitt

modulated

g changes

f the anima

ns. The si

mal’s cage

eart rate, b

d from all e

The polys

ersion 2.0.

f-line in 10

to aid in d

presence

range (0.5

ement (RE

minance of

ck of mus

rregular low

s. The am

ks. The de

ast Fourrie

hs and was

ed only for

phase. Du

analysed.

aquest A.R

d polysom

ed blood p

d signals. T

s in the re

als. Heart

ignals wer

and were

blood press

eight anima

somnograp

.0 (DataSc

0-s epochs

discriminat

of high a

5-4 Hz) an

M) sleep w

f theta acti

scle tone

w-amplitud

mount of tim

elta power

er Transfor

s expresse

r the 1.5-h

e to artefa

R.T. Syste

mnograph

pressure, b

The gross

eceived sig

rate value

re received

e processe

sure, body

als in 10-s

phic bio-po

ciences In

s. A concu

ting betwe

amplitude

nd low mus

was charac

ivity (4.5-8

with occ

de, fast EE

me spent

during NR

rmation (FF

ed as perce

h post-dep

acts in the

m (DataS

ic signals

body tempe

locomotor

gnal streng

es were ca

d by an a

ed by a co

y temperat

epochs an

otential rec

nternationa

urrent EEG

en states.

EEG wav

scle tone a

cterized by

Hz) with r

casional tw

EG, higher

in each v

REM sleep

FT) at a res

entage of t

privation re

e EEG sig

ciences

s were

erature,

r activity

gth that

lculated

antenna

omputer

ure and

nd were

cordings

al). The

G power

NREM

ves and

and lack

y highly

reduced

witches.

muscle

igilance

p in the

solution

the total

ecovery

nals for

Blood

Blood w

vein ca

proced

every 1

frequen

novelty

stored

Subseq

corticos

Cortico

ng/ml.

Statist

For all

evaluat

the Gre

varianc

animals

betwee

for the

the nov

study t

on the

analyse

depriva

novelty

did not

the ana

phase

Since t

sampling

was sampl

atheter in

ures to mi

10 – 120 m

ncy during

y to be ab

inside th

quently, p

sterone

osterone125

ics

measurem

ted with tw

eenhouse-

ce. Even th

s was not

en-subjects

sleep dep

velty expos

he effect o

response

es did not

ation and

y phase se

give a diff

alyses don

and for t

there was n

and assa

led using t

both stu

nimize pos

min in sma

g the reco

ble to mon

he machin

plasma w

with a 5I RIA Kit, M

ments, the

wo-way an

-Geisser c

hough a c

always pre

s factor rat

rivation pe

sure perio

of sleep de

es to nove

show sign

post-depri

eparately, i

ference in

ne for the s

he novelty

no significa

ays

he automa

udies. Anim

ssible stres

ll sample v

overy of s

nitor the re

ne at 4°C

as stored

double

MP Biome

e effect of

alysis of v

correction

ross-over

esent in bo

ther than

eriod with s

od with sub

eprivation i

elty during

nificant effe

vation pha

in order to

significanc

sleep depr

y exposure

ant differen

Sle

ated blood

mals were

ss-confoun

volumes of

sleep depr

esponse to

C until ce

d at –80°

antibody

edicals, So

f sleep de

variance (A

epsilon (ε)

design wa

oth groups

as a within

subsequen

bsequent 7

itself and t

g the diffe

ects, the a

ase separ

o check for

ce, the res

rivation pe

e period w

nce betwee

eep depriva

sampling

e habituat

nding effec

f 30-µl. Sa

rivation, n

o novelty

entrifuged

°C until

y radioim

lon, OH, U

privation a

ANOVA) w

) for putat

as initially

s. Therefor

n-subject f

nt 1.5-h pos

75-min pos

then for the

erent time

analyses w

rately, and

r an effect

ults are on

riod with s

with subse

en the nov

ation and

system an

ed to the

cts of it. Bl

amples we

ovelty exp

closely. Th

for 5 mi

assayed

mmunoass

USA) with a

and novelt

with repeate

tive lack o

used, the

re, treatme

factor. Ana

st-deprivat

st-novelty

e effect of

periods.

were also d

d for the n

t in the rec

nly shown

subsequen

equent po

velty and no

d novelty ex

nd the dual

e blood sa

ood was s

re taken a

posure an

he sample

n at 321

in duplic

say (Mou

a sensitivit

ty exposur

ed measu

of homoge

data of th

ent was us

alyses wer

tion phase

phase in o

sleep dep

If these A

done for th

novelty an

covery. Sin

and discus

nt post-dep

ost-novelty

on-novelty

xposure

79

l jugular

ampling

sampled

t higher

d post-

es were

0 rpm.

ate for

use/Rat

ty of 3.0

re were

res and

neity in

e same

ed as a

re done

and for

order to

privation

ANOVA

he sleep

nd post-

nce this

ssed for

privation

phase.

y control

Chapte

80

conditio

that tim

control

found f

novelty

taken t

what ti

post-de

differen

were ta

inc., Ch

are pre

RESUL

Experi

respon

Sleep d

Data o

corticos

the 1.5

respect

were re

For loc

depriva

depriva

activity

5 min a

conditio

signific

er 4

on prior to

me frame a

and sleep

for the no

y-exposed

together d

me points

eprivation

nce betwee

aken toget

hicago, IL,

esented as

LTS

ment 1:

nses to 4 h

deprivation

on locomo

sterone du

5-h post-de

tively). Un

eached for

comotor ac

ation intera

ation effec

levels we

after termin

on. Twenty

antly below

o the actua

and analys

p-deprived

ovelty expo

(sleep-dep

uring this

novelty a

and post

en novelty

her. All an

USA). All

mean + S

Dynamics

h of sleep

n and cons

otor activit

uring 4-h s

eprivation

nder non-d

all measu

ctivity, repe

action (F67

ct (F1,24=40

re increas

nation of th

y min later

w control le

al novelty e

sed by po

d differed.

osure perio

prived and

period an

nd non-no

t-novelty e

y and the

nalyses we

tests were

SEM.

s of the

deprivati

secutive rec

ty, heart

leep depriv

recovery

deprived co

rements

eated mea

,1608=10.2,

0.0 p<0.00

ed during

he sleep de

r, locomoto

evels for 2

exposure,

ost-hoc t-te

Also, sinc

od and the

control) a

d analysed

ovelty diffe

exposure

non-novelt

ere perform

e performe

behaviou

on with su

covery

rate, bloo

vation or th

phase are

ontrol con

asures ANO

ε=0.1, p<

01). Post-h

the whole

eprivation

or activity i

0 min.

these grou

ests to det

ce no effec

e post-nov

and non-no

d by post-

ered. For N

periods a

ty control

med using S

ed at a sign

ural, phys

ubsequen

od pressur

he non-de

e illustrate

ditions, af

OVA revea

<0.001) and

hoc analy

sleep dep

procedure

n the sleep

ups were t

termine at

ct of sleep

velty expo

ovelty expo

-hoc t-tests

NREM delt

are show

condition

SPSS 15.0

nificance le

siological

t novelty e

re, body

prived con

d in Figur

fter lights-o

aled a sign

d a signific

sis showe

privation pe

e as compa

p-deprived

taken toge

what time

p deprivati

osure phas

osed group

s to deter

ta power o

n and sin

was found

0 software

evel of 0.0

l and ho

exposure

temperatu

ntrol condit

re 1 (pane

on, stable

nificant tim

cant overa

ed that loc

eriod until

ared to the

d animals d

ether for

e points

on was

se, both

ps were

mine at

only the

nce no

d, these

e (SPSS

05. Data

ormonal

ure and

tion and

els A-E,

values

e*sleep

all sleep

comotor

the first

e control

dropped

Also fo

(F67,1608

p=0.00

to the n

period.

decrea

For blo

(F67,1608

which t

For bod

(F67,1608

p=0.02

depriva

sleep d

Plasma

Novelty

Figure

temper

control

75-min

conditio

or brief

room.

ANOVA

(F18,432=

but no

levels

termina

For he

p<0.00

rate re

or heart rat

8=4.9, ε=0

8). Sleep d

non-depriv

Upon te

sed to con

ood pressu

8=2.9, ε=0

the sleep-d

dy tempera

8=2.8, ε=0

9). Body te

ation and g

deprivation

a corticoste

y exposure

1 also s

rature and

conditions

post-nove

ons, a slig

fly after th

A showed

=13.9, ε=0

effect of p

stayed el

ation of nov

eart rate

1) and a s

esponse to

te, ANOVA

0.1, p<0.00

deprivation

ved control

ermination

ntrol levels

ure, ANOV

0.2, p=0.00

deprived an

ature ANO

0.1, p=0.01

emperature

gradually r

procedure

erone leve

e and cons

shows the

corticoster

s starting 1

elty phase

ht but non

he novelty

that novel

0.2, p<0.00

rior sleep d

levated du

velty.

levels a

significant

o novelty w

A revealed

01) and a

n induced

condition

of the sl

within 5 m

VA showed

02). Post-h

nd non-dep

OVA showe

15) and a

e reached

returned to

e.

ls were no

secutive rec

e locomoto

rone respo

1.5 h after

(panels A

n-significan

exposure

lty exposu

01) and a

deprivation

uring expo

significant

novelty eff

was not a

Sle

d a signific

a significan

a significa

during mo

leep depr

min.

d a signific

hoc analys

prived con

ed a signific

a significan

significant

o control l

ot significan

covery

or activity

onses to 15

the termin

A-E, respec

nt increase

experienc

re induced

significan

n on locom

osure to

t time*nov

fect (F1,24=

affected by

eep depriva

cant time*s

nt sleep d

nt increase

ost time po

ivation pro

cant time*s

is howeve

trol conditi

cant time*s

nt sleep d

tly higher l

evels 20 m

ntly affecte

y, heart ra

5-min nove

nation of s

ctively). Un

e in all mea

ced by the

d a signific

nt novelty

motor activi

the nove

velty intera

20.7, p<0.

y prior sle

ation and

sleep depr

eprivation

e in heart

ints of the

ocedure,

sleep depr

er showed

ion signific

sleep depr

eprivation

evels after

min after t

ed by sleep

ate, blood

elty exposu

leep depriv

nder the no

asurement

other anim

cant time*n

effect (F1,2

ty levels. L

l cage un

action (F1

.001) were

eep depriv

d novelty ex

ivation inte

effect (F1

rate as co

sleep dep

heart rate

ivation inte

no time p

cantly differ

rivation inte

effect (F1

r 100 min o

termination

p deprivatio

d pressure

ure or non-

vation and

on-novelty

ts is visible

mals in th

novelty inte

24=25.9, p

Locomotor

ntil 15 mi

8,432=12.4,

e found. Th

vation. Hea

xposure

81

eraction

1,24=8.5,

mpared

privation

e levels

eraction

points at

red.

eraction

1,24=5.4,

of sleep

n of the

on.

e, body

-novelty

d for the

y control

e during

e same

eraction

<0.001)

r activity

in after

ε=0.3,

he heart

art rate

Chapte

82

values

compa

For b

(F18,432=

hoc an

novelty

For bo

was fou

signific

already

conditio

this tem

Finally,

(F1,24=2

levels

end of

er 4

were incr

rable to the

lood pres

=9.6, ε=0.2

nalysis onl

y control co

dy temper

und. Body

antly highe

y returned

on were re

mperature

, for plasm

20.3, p<0.0

increased

the novelty

reased du

e non-nove

ssure, AN

2, p<0.001

ly showed

ondition 5 m

rature a si

temperatu

er levels 1

d to their

eached aga

response.

ma corticost

001) but no

slowly du

y exposure

uring expo

elty conditi

NOVA sh

1) but no e

d a signific

min after te

ignificant t

ure slowly

10 min afte

home ca

ain after 2

terone leve

o effects o

ring novel

e, which th

osure to n

ion 30 min

owed a

effects of t

cant differ

ermination

time*novelt

increased

er terminat

ages. Lev

0 min. Prio

els, ANOV

of prior slee

ty, reachin

en remain

novelty and

after term

significan

the sleep

ence betw

of novelty

ty effect (F

during nov

tion of nov

vels comp

or sleep de

VA revealed

ep depriva

ng significa

ed elevate

d graduall

mination of

nt time*no

deprivation

ween the

y.

F18,432=4.8

velty expo

velty when

parable to

eprivation

d a signific

ation. Plasm

antly eleva

ed for 20 m

ly reached

novelty.

ovelty inte

n condition

novelty an

8, ε=0.2, p

sure and r

n the anim

the non-

had no eff

cant novelt

ma cortico

ated levels

min.

d levels

eraction

n. Post-

nd non-

=0.003)

reached

als had

-novelty

fects on

ty effect

osterone

s at the

He

art r

ate

(bp

m)

320340360380400420440460

Blo

od p

ress

ure

(mm

Hg

)

95

105

115

125

Bod

y te

mpe

ratu

re (

°C)

37,5

38,0

38,5

39,0

39,5

Cor

ticos

tero

ne (

ng/m

l)

0

40

80

120

160

Act

ivity

(co

unts

/min

)

0

5

10

15

20

Figure 1(panel Cperiod ((indicateexposurpost-novmeasureare showwithout deprivat30-min r*p<0.05

-20 0 20

-20 0 20

-20 0 20

*

-20 0 20

A

B

C

D

E

1. Time courC), body temp(i.e. last 15 ed by the arere to novelty velty periodements and wn for the nnovelty expotion with novrise (grey) an, novelty vers

40 60 80

40 60 80

40 60 80

40 60 80

* * *

ControContro

rse of changeperature (pamin of dark

ea between or non-nove

d. Data areas 10-120 m

non-deprivedosure (n=6), velty exposurnd light (whitsus non-nov

100 120 140

100 120 140

100 120 140

100 120 140

*

*** ***

ol + non-noveol + novelty

es in locomonel D) and pk period), ththe dashed elty (indicatee expressedmin mean vad control connon-deprive

re (n=8). Thete) period. S

velty, #p<0.05

Sle

160 180 200

160 180 200

160 180 200

Time

160 180 200

*

*

elty

otor activity (plasma cortiche 4-h sleeplines), the 1

ed by the ard as 5-minalues + SEMndition withod control cone bars underignificance: 5.

eep depriva

220 240 260

220 240 260

220 240 260

(min)

220 240 260 2

*

SD + noSD + no

panel A), heosterone (pap deprivation.5-h recoverea between

n averages for the cort

out novelty endition with nrneath the grsleep depriv

ation and

280 300 320

280 300 320

280 300 320 3

280 300 320 3

*

on-noveltyovelty

eart rate (pananel E) durinn or non-dery period anthe dotted l+ SEM fo

icosterone mexposure (n=novelty exporaph indicate

vation versus

d novelty ex

340 360 380 4

340 360 380 4

340 360 380 40

40 360 380 40

#

#

#

#

#

nel B), bloodg the 15-minprived contrd subsequenlines) and thor the phy

measuremen=8), sleep deosure (n=6) ae the dark (bs non-deprive

xposure

83

00 420 440

00 420 440

00 420 440

00 420 440

pressuren baselinerol periodnt 15 minhe 75-minysiologicalts. Theseeprivationand sleepblack); theed control

Chapte

84

Experi

respon

Sleep d

Locomo

sleep d

depriva

deprive

measu

Sleep d

p=0.00

ε=0.1, p

locomo

termina

within 5

For bo

interact

depriva

levels a

during

depriva

Plasma

Novelty

Figure

corticos

conditio

post-no

locomo

signific

same r

er 4

ment 2:

nses to 6-h

deprivation

otor activit

deprivation

ation recov

ed control c

rements

deprivation

1) and ind

p=0.04). P

otor activit

ation of the

5 min.

ody temp

tion (F91,13

ation effect

after 40 m

the rema

ation proce

a corticoste

y exposure

2 also

sterone re

ons startin

ovelty phas

otor activit

antly affec

room.

Dynamics

h sleep de

n and cons

ty, body te

n or the no

very are illu

conditions

n affected

duced a s

Post-hoc an

y levels t

e sleep de

perature, A

365=3.1, ε=

t (F1,15=3.4

min of slee

ainder of

edure, cont

erone leve

e and cons

shows th

esponses

g 1.5 h aft

se (panel

y, body te

cted by the

s of the

eprivation

secutive rec

mperature

on-deprive

ustrated in

, after the

the locom

significant

nalysis sho

throughout

eprivation

ANOVA s

=0.1, p=0.

4, p=0.087)

p deprivat

the sleep

trol temper

ls were un

secutive rec

he locomo

to 15-m

ter the term

A-C, resp

emperatur

e novelty ex

behaviou

with subs

covery

e, and plas

d control c

n Figure 2

lights-on c

motor activ

time*sleep

owed that t

t most of

procedure

showed a

.007) and

). Body tem

tion and st

p deprivati

rature leve

naffected b

covery

otor activi

in novelty

mination of

ectively). U

e and pla

xposure ex

ural, phys

sequent n

ma cortico

condition a

(panel A-C

cue, stable

vity respon

p deprivati

the sleep-d

the sleep

e, control a

a significa

a close

mperature

tayed elev

ion. Upon

ls were rea

y sleep de

ty, body

y exposur

f the sleep

Under non

asma corti

xperienced

siological

novelty exp

osterone re

and subse

C, respecti

values we

nse signific

on interac

deprived ra

p deprivati

activity lev

ant time*s

to signific

reached s

vated at se

n terminati

ached with

eprivation.

temperatu

re or no

deprivatio

n-novelty c

icosterone

d by the oth

l and ho

posure

esponses t

equent 1.5-

vely). Und

ere reache

cantly (F1,1

ction (F91,1

ats had inc

ion period

els were r

sleep dep

ant overa

significantly

everal time

ion of the

hin 5 min.

ure and

n-novelty

n, and the

control con

levels w

her animal

ormonal

o 6 h of

-h post-

der non-

ed for all

15=17.1,

365=2.2,

creased

d. Upon

reached

privation

ll sleep

y higher

e points

e sleep

plasma

control

75-min

nditions,

ere not

ls in the

Novelty

p<0.00

sleep

increas

levels 1

For bo

p<0.00

case, a

interact

gradua

animals

45 min

novelty

For pl

p=0.00

sleep d

novelty

y exposure

1) and a s

deprivation

sed throug

15 min afte

ody tempe

1) and a

a significan

tion with n

ally increas

s returned

n later. Fu

y, had lowe

asma cor

6) and a s

deprivation

y until 30 m

e induced

significant

n on loco

ghout the e

er terminat

erature a

significant

nt sleep de

novelty eff

sed during

to their ho

rthermore

er body tem

rticosteron

significant

n were fou

min afterwa

a significa

overall ef

omotor ac

exposure

ion of nove

significant

t novelty e

eprivation e

ffects. Pos

novelty, r

ome cages

, the sleep

mperature

e a sign

novelty ef

und. Plasm

ards.

Sle

ant time*no

ffect (F1,15=

ctivity leve

to novelty

elty.

t time*nov

effect (F1,1

effect was

st-hoc ana

reaching s

s. Non-nov

p-deprived

levels at se

nificant tim

ffect (F1,15=

ma corticos

eep depriva

ovelty inte

=97.3, p<0

els. Locom

y and retur

velty intera

5=10.4, p=

also found

alysis show

significantly

elty contro

d animals,

everal time

me*novelty

=7.7, p=0.0

sterone lev

ation and

raction (F1

0.001) but

motor act

rned to no

action (F1

=0.006) we

d (F1,15=9.0

wed that b

y elevated

ol levels we

regardles

e points.

effect (F

014) witho

vels were

d novelty ex

18,270=26.6

no effect

ivity level

on-novelty

8,270=12.7,

ere found.

0, p=0.009

body temp

d levels wh

ere reache

ss of expo

F8,120=4.6,

out effects

increased

xposure

85

, ε=0.3,

of prior

s were

control

ε=0.3,

In this

) but no

perature

hen the

ed again

osure to

ε=0.4,

of prior

d during

Chapte

86

Figure 2plasma 6-h sleethe 1.5-(indicateexpressevalues +conditiondeprived(n=5). Tperiod. novelty,

Bod

y T

empe

ratu

re (

C)

36,5

37,0

37,5

38,0

38,5

39,0

Cor

ticos

tero

ne (

ng/m

l)

0

50

100

150

200

Act

ivity

(co

unts

/min

)

0

5

10

15

20

25

30

er 4

2. Time coucorticosteronp deprivation-h recovery ed by the aed as 5-min+ SEM for thn without nod control conhe bars undeSignificance#p<0.05.

*

-20 20

-20 20

A

B

C

rse of changne (panel C) n or non-depperiod and

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** *

60 100

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ControContro

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140 180

*

140 180

ol + non-noveol + novelty

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***

****

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*

220 260

*

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Time (m

220 260

elty

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(black); the 3prived contro

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300 340

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300 340

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380 420

***

380 420

on-noveltyovelty

erature (panein of dark pe

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#

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Figure 3REM sledeprivatirecoverybetween+ SEM adeprivatiand slee(black); deprived

-20 20

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3. Time courseep (panel Cion or non-dey period andn the dotted land are shoion without nep deprivatiothe 30-min

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140 180

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elty

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ation and

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40 380 4

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87

500 540

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el B) and6-h sleepthe 1.5-hthe area

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rsus non-

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88

Experi

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Sleep d

The am

depriva

respect

asleep.

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concom

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p<0.00

sleep a

p<0.00

p<0.00

(F29,638=

p<0.00

affected

within 1

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sleep s

depriva

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Figure

15-min

termina

Exposu

decrea

ANOVA

and a

sleep d

er 4

ment 2. C

nse to 6 h

deprivation

mount of w

ation or no

tively). Und

.

deprivatio

mitant redu

A showed

1) and a s

a significan

1) togethe

1). For R

=5.6, ε=0.

1) were fo

d during t

15 min upo

but signif

stable cont

ation proce

y exposure

3 also sho

novelty e

ation of the

ure to nove

se in time

A showed

significant

deprivation

Changes i

of sleep d

n and cons

wakefulness

on-deprived

der non-de

n significa

uction in t

a significa

significant s

nt time*sle

er with an

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3, p<0.001

ound. The

the sleep

on termina

ficantly inc

trol levels w

edure.

e and cons

ows the am

exposure o

e sleep dep

elty signific

e spent in

a significa

novelty e

n treatmen

in sleep-w

deprivatio

secutive rec

s, NREM s

d control c

eprived con

antly incre

time spent

ant time*sl

sleep depr

eep depriva

overall s

p also a

1) and a s

e time spe

deprivatio

ation of the

creased at

were reach

secutive rec

mount of w

or non-nov

privation, a

cantly incre

NREM an

ant time*n

ffect (F1,22

nt. For NR

wake distr

n with sub

covery

sleep and

conditions

ntrol condi

eased the

t in NREM

eep depriv

rivation effe

ation intera

ignificant

significan

significant

ent in wak

n period a

e sleep dep

30 - 45 m

hed within

covery

wakefulness

velty contr

and the 75-

eased the

nd REM s

novelty inte

2=15.1, p=

EM sleep,

ribution a

bsequent

REM sleep

is illustrat

tions, anim

time spe

M and RE

vation inte

ect (F1,22=4

action was

sleep dep

nt time*sle

sleep dep

kefulness a

and return

privation p

min after s

30 min up

s, NREM s

rol conditio

-min post-n

time spen

leep. For

eraction (F

0.001) but

a signific

and NREM

novelty ex

p during a

ted in Figu

mals spent

ent in wa

M sleep.

eraction (F2

416.4, p<0

s found (F2

privation ef

eep depriv

privation ef

and NREM

ned to sta

rocedure.

sleep depr

pon termin

sleep and R

ons startin

novelty pha

nt awake w

time spen

F5,110=22.5

t no effect

cant time*n

M delta po

xposure

nd after 6-

ure 3 (pan

most of th

kefulness

For wakef

29,638=23.0

0.001). For

29,638=23.6

ffect (F1,22

vation inte

ffect (F1,22

M sleep w

ble contro

NREM sle

rivation. Fo

nation of th

REM sleep

g 1.5 h a

ase.

with a conc

nt in wakef

, ε=0.7, p

t of the pre

novelty inte

ower in

-h sleep

nel A-C,

heir time

with a

fulness,

, ε=0.3,

r NREM

, ε=0.3,

=332.4,

eraction

=140.3,

as only

ol levels

eep was

or REM

he sleep

p during

after the

comitant

fulness,

<0.001)

eceding

eraction

Figure percentapost-sleemin postdeprived(n=7), nexposure(n=8) anare exprdeprivati

(F5,110=

p=0.00

also a

signific

depriva

signific

increas

returne

termina

compa

novelty

DISCU

The aim

physiol

NR

EM

del

ta p

ower

(%

tot

al p

ower

)

0

10

20

30

40

50

60

4. The NRage of the toep deprivatiot-novelty perd control conon-deprivede (n=6), slend sleep depressed as mion versus no

=22.6, ε=0

6) were fo

a significa

ant novelt

ation was

antly incre

se was pa

ed to levels

ation of n

red to the

y.

SSION

m of the pr

ogical and

*

post

REM delta potal power ison recovery priod. These andition witho

d control coeep deprivaprivation with

means + SEMon-deprived

.7, p<0.00

ound but a

nt time*n

ty effect

found. Po

eased throu

aralleled by

s comparab

novelty. Fu

non-nove

resent stud

d hormon

t-SD

ControlControlSD + nSD + n

power expres shown for period and fo

are shown foout novelty ondition withation withouh novelty (nM. *type effecontrol, p<0

01) togeth

again no ef

ovelty int

(F1,22=17.9

ost-hoc ana

ughout the

y a signifi

ble to the n

urthermore

elty conditio

dy was to a

al measu

*

post-novelt

l + non-novell + noveltyon-noveltyovelty

Sle

essed as the 1.5-h

or the 75-r the non-exposure

h novelty ut novelty =5). Data ect: sleep .05

her with a

ffect of pri

eraction (

9, p<0.001

alysis sho

e novelty e

icant redu

non-novelt

e, for REM

on was fo

assess how

res, indica

ty

ty

eep depriva

significan

ior sleep d

(F5,110=2.7

1) but wit

owed that

exposure u

ction in N

ty control c

M sleep,

und 45 - 6

The delta

expresse

power

deprivatio

during

phase is

ANOVA

deprivatio

p=0.012)

effect of

hoc ana

increase

sleep de

deprivatio

novelty ex

w 4 and 6

ative of s

ation and

nt novelty

deprivation

, ε=0.8, p

thout effec

the time s

until 15 min

NREM and

condition w

a signific

60 min up

a power du

ed as perce

during th

on recov

the 75-m

s illustrate

showed a

on effe

) but there

the novelty

lysis show

in NREM

eprivation

on and d

xposure ph

h of sleep

sympathetic

d novelty ex

effect (F1

. For REM

p=0.039)

ct of prio

spent awa

n afterward

REM sle

within 30 m

ant reduc

pon termin

uring NREM

entage of t

he 1.5-h

ery phas

min post-

ed in Fig

a significan

ect (F1

was no ad

y exposure

wed a sig

M delta po

during the

during the

hase.

deprivatio

c and HP

xposure

89

1,22=9.4,

M sleep,

with a

r sleep

ake was

ds. This

eep that

min upon

ction as

ation of

M sleep

the total

post-

se and

-novelty

gure 4.

nt sleep

1,22=7.4,

dditional

e. Post-

gnificant

ower by

e post-

e post-

on affect

PA axis

Chapte

90

activity

system

high-fre

samplin

were ta

deprive

observa

pressu

through

der Gu

deprive

T

depriva

short a

comple

unavoid

pressu

depriva

reboun

signific

control

post-sle

sleep d

et al.,

during

that rep

Neuhau

handlin

are still

S

heart r

blood p

(Axelro

er 4

, and how

ms to novel

equency in

ng and sle

aken durin

ed control

ation perio

re and bod

hout most

ugten, 198

ed control c

The polys

ation effect

and scatte

etely suppr

dable duri

re during

ation proce

d afterwar

ant increa

condition.

eep depriv

drive and a

1991; Borb

the post-n

ported in p

us, 1979;

ng procedu

l detectabl

Sleep dep

rate, blood

pressure in

od and Reis

w sleep dep

ty exposur

n freely mo

eep depriv

ng the ligh

conditions

od. Furthe

dy temper

of the cont

87). Taken

conditions

somnograp

tively prev

ered NREM

ressed The

ing sleep

deprivatio

edure is

rds. Furthe

ase in NRE

. Also, the

vation reco

an indicato

bely, 1998

novelty exp

previous s

McKenna

ure was suf

e after nov

rivation ind

d pressure

n response

sine, 1984

privation a

re. The pa

oving rats,

ation proc

t phase; t

the anima

ermore, no

ature and

trol conditi

n together

were not a

phic record

vented rats

M microsle

e short NR

deprivatio

on(Friedma

also confi

ermore, 30

EM sleep

delta pow

overy perio

or of sleep

8). This inc

posure ph

studies usi

et al., 200

fficient to d

velty expos

duced mild

and body

e to sleep d

4; Johnson

affects the

rameters w

while redu

cedure as

he circadia

als indeed

ormal and

also of pla

on (Buttne

r, this sug

affected by

dings con

s from sle

eeps were

REM micro

on and are

an et al.,

irmed by

0 – 45 mi

was visib

wer during

d, which is

intensity (

creased N

ase. This

ng short s

08). Thus, 6

deprive rat

sure.

d, temporal

y tempera

deprivation

et al., 199

subseque

were meas

ucing stres

much as p

an resting

were inac

d stable le

asma corti

er and Wol

ggests tha

y the samp

firm that

eping. Du

observed

osleeps tha

e an indic

1979). T

the occur

in after sle

ble as com

NREM sle

s considere

Borbely an

REM delta

compensa

sleep depr

6 h of slee

ts from sle

l increases

ture. The

n are indic

92), which

ent reactivit

sured simu

s-confound

possible. A

phase in

ctive and a

evels of h

icosterone

lnik, 1982;

at the ani

pling proce

6-h gentle

ring sleep

d whereas

at were se

cation for

The effica

rrence of

eep depriv

mpared to

eep was el

ed a marke

nd Neuhau

a power w

atory respo

ivation in

ep depriva

ep and to

s in gross l

increase

cative of sy

may also b

ty of these

ultaneously

ding effect

All measur

rats. Und

asleep mos

heart rate

e were mai

De Boer a

mals unde

dures.

e handling

deprivatio

REM sle

een are pra

increasing

acy of ou

a compe

vation, a m

the non-d

evated du

er for home

us, 1979; F

was also ob

onse is si

rats (Borb

tion by ou

cause effe

ocomotor

in heart ra

ympathetic

be respons

e stress

y and at

ts of the

rements

er non-

st of the

, blood

intained

and van

er non-

g sleep

on, only

ep was

actically

g sleep

r sleep

ensatory

mild but

deprived

ring the

eostatic

Franken

bserved

milar to

ely and

r gentle

ects that

activity,

ate and

activity

sible for

the mild

activity

depriva

activati

and al

compa

Tochiku

levels w

studies

et al.,

Hipolid

increas

cortisol

1992).

be con

in loco

control

addition

during

levels d

circadia

and Wo

respon

within 2

rapid d

a slowe

with the

which

1984; J

temper

periphe

mildly

d but grad

is necess

ation (Lea

on is in a

lso higher

red to duri

ubo et al.,

were not a

s showed i

1996; Su

e et al., 2

ses were m

l or cortico

Also the

sidered mi

omotor act

situation a

n, it maint

the last 15

did not ex

an cycle u

ollnik, 1982

ses showe

20 min. In

ecline to c

er decline.

e knowledg

have imm

Johnson e

rature will

eral vasoco

and reco

dual increa

ary to supp

al-Cerro e

agreement

r heart ra

ng sleep in

1996; Irwi

affected by

ncreased

checki et

006; Sgoif

moderate a

osterone le

SAM activ

ild. In fact,

tivity, hear

at the beg

ained leve

5 min of th

xceed the

nder home

2). Upon te

ed differen

general, h

control valu

The rapid

ge that SA

ediate effe

et al., 1992

change

onstriction

overy occu

ase in body

port the wa

et al., 200

with othe

ate and b

n both anim

in et al., 19

y short slee

glucocortic

al., 1998;

fo et al., 2

and various

evels at a

vation in re

sleep dep

rt rate and

ginning of t

els compar

he dark pe

average v

e cage con

ermination

nt time cou

heart rate,

ues upon t

d decline in

AM activati

ects on the

2). For bod

due to c

. Altogethe

urred with

Sle

y temperat

akefulness

03). Furth

er studies

blood pres

mals and h

999; Sforz

ep deprivat

coid levels

; Spiegel

2006; Meer

s other stu

all (Rechtsc

esponse to

privation ap

d body tem

the light p

rable to th

eriod prece

values obs

nditions as

n of the sle

urses but

blood pres

termination

n heart rate

on results

e cardiova

dy tempera

changes i

er, sleep d

hin 20 m

eep depriva

ture. Such

s and activi

hermore, t

showing h

ssure leve

humans (A

za et al., 20

tion. While

s during sle

et al., 19

rlo et al., 2

udies foun

chaffen et

sleep dep

ppeared to

mperature

hase, i.e.,

e normal w

eding sleep

erved duri

s reported

eep depriva

all returne

ssure and

n, whereas

e and bloo

in a rapid

ascular sys

ature a de

n metabo

deprivation

in upon

ation and

an increa

ity associa

the obser

higher cate

els during

kerstedt an

004). Plasm

e several h

eep depriv

99; Chapo

2008), in m

nd no sign

t al., 1983

privation in

o prevent th

that was

circadian

waking lev

p deprivati

ing the ac

in previous

ation proce

ed to resti

locomotor

s body tem

od pressur

release o

stem (Axe

elay was e

olism, mus

n affected

termination

d novelty ex

se in symp

ated with th

rved symp

echolamine

wakefuln

nd Froberg

ma cortico

human and

vation (von

otot et al.

most case

ificant cha

; Follenius

n our study

he normal

observed

resting ph

vels as me

on. Indeed

ctive phase

s studies (

edure, the

ng control

activity sh

mperature s

re is in agr

of catechola

lrod and R

expected, a

scle activ

the SAM

n. Moreov

xposure

91

pathetic

he sleep

pathetic

e levels

ness as

g, 1979;

osterone

d animal

n Treuer

, 2001;

s these

anges in

s et al.,

y should

decline

d in the

hase. In

easured

d, these

e of the

(Buttner

various

values

howed a

showed

reement

amines,

Reisine,

as body

ity and

system

ver, no

Chapte

92

differen

temper

A

laborat

sleep lo

used to

depriva

above t

terms o

not affe

stress.

end of

agitatio

after sl

Whethe

sleep lo

the end

system

sleep d

depriva

I

a new

include

2006).

respon

period

altered

but we

Novelty

pressu

and bl

increas

reachin

er 4

nces betwe

rature and

A commo

ory anima

oss per se

o sleep de

ation metho

those reac

of glucoco

ected. In t

On the oth

the sleep

on specifica

leep depriv

er this is a

oss per se

d of the sle

m activation

debt and ti

ation metho

In order to

challenge

ed before

As the r

se to slee

and there

basal leve

ere not in

y exposur

re, body te

ood press

ses in bo

ng significa

een 4 and

plasma co

on issue

als is that t

e, but fully o

eprive the

od just ca

ched during

orticoid rele

that sense

her hand, s

deprivatio

ally, hypera

vation (Hic

direct con

e remained

eep depriv

n. This sug

redness, r

od but futu

o study effe

e, an undis

rats were

esults sho

ep deprivat

efore the s

els. The an

an agitat

re induced

emperature

sure incre

dy tempe

ance only

6 h of slee

orticosteron

of discus

the observ

or partly d

animals (

used a mi

g normal w

ease as o

e, our met

some rats

n session.

activity and

cks et al.,

nsequence

d unclear. I

vation sess

ggests that

rather than

ure studies

ects of prio

sturbed re

exposed

ow, all ph

tion had re

subsequen

nimals und

ted state

d an incre

e and plasm

ased imm

erature an

by the en

ep depriva

ne levels w

ssion rega

ved effects

ue to the s

(Meerlo et

ld activatio

wakefulnes

only plasma

hod was n

appeared

Even thou

d increase

1979; Ge

of the met

Interesting

sion and w

this agitat

n a conseq

are neede

or sleep de

ecovery pe

to novelty

hysiologica

eached co

nt novelty

der sleep-d

anymore

ease in lo

ma cortico

mediately u

d plasma

nd of the

ation on gro

were obser

arding sle

s may not

stressful co

t al., 2008

on of the S

ss. Moreov

a corticost

not associ

to be in a

ugh publis

ed aggress

ssa et al.,

thod used

ly, this agi

was not refl

tion may b

quence of s

ed to confir

eprivation o

eriod follow

y (Meerlo

l and beh

ontrol leve

responses

deprived co

when exp

ocomotor

sterone. L

upon nove

corticoste

novelty ex

oss locom

rved.

eep depriv

only be a

omponents

8). As disc

SAM syste

ver, the HP

terone wa

ated with

n agitated

shed studie

iveness ha

1995; Ta

to induce

tation was

lected in a

e the resu

stress indu

rm this.

on subsequ

wing sleep

et al., 200

havioural m

ls within th

s were no

onditions h

posed to n

activity, h

ocomotor

elty expos

erone we

xposure o

otor activit

vation stu

a conseque

s of the pro

cussed, ou

em with lev

PA axis, at

s measure

a high de

state towa

es do not m

ave been r

artar et al.,

wakefulne

s only obse

a change in

lt of accum

uced by th

uent respo

p deprivati

02; Sgoifo

measurem

his brief re

ot confoun

had a sleep

novelty ex

heart rate

activity, he

sure where

re much

or even wh

ty, body

dies in

ence of

ocedure

ur sleep

vels not

least in

ed, was

egree of

ards the

mention

eported

, 2008).

ess or of

erved at

n stress

mulating

he sleep

onses to

on was

o et al.,

ments in

ecovery

nded by

p deficit

xposure.

, blood

eart rate

eas the

slower,

hen the

animals

novelty

exposu

were c

(Chapte

and HP

subseq

agreem

affect t

inescap

SAM sy

also sh

restrict

Novati

on str

physiol

prolong

O

to depr

exposu

behavio

unaffec

subseq

as mea

does n

sleep lo

ACKNO

The au

Kieboo

assista

s were al

y control c

ure for all

comparable

er 2). Clea

PA axis w

quent 1.5

ment with p

the corticos

pable foot

ystem was

howed tha

ion gradua

et al., 200

ress reac

ogical and

ged sleep d

Overall, 6

rive rats fr

ure. The p

oural activ

cted. We fu

quent neur

asured 1.5

not affect s

oss.

OWLEDGE

uthors wou

om, Heidi H

ance.

ready retu

conditions w

measurem

e with thos

arly, physi

were activ

h recove

previous st

sterone an

shock stre

s also unaf

at a longe

ally lead t

08). It was

ctivity may

d hormon

deprivation

h of sleep

om sleep

resent stu

vity and is

urthermore

roendocrin

h after sle

stress sys

EMENTS

uld like to

Huysmans

urned to t

were reac

ments. The

se reporte

cal activity

ated, yet,

ery did no

tudies repo

nd ACTH r

ess (Meerl

ffected was

er duration

to an atte

therefore

y accumu

al respon

n remains t

p deprivatio

and to cau

udy also sh

a mild act

e conclude

e and phy

eep depriv

stem react

thank Lee

, An Torre

Sle

heir home

ched within

ese pattern

ed in our p

y was indu

previous

ot affect t

orting that

response t

o et al., 20

s not addr

n of total

enuated AC

suggested

ulate ove

ses to no

to be studi

on by our g

use effects

hows that

ivator of th

e that acute

ysiological

vation term

tivity to no

n Raeyma

emans and

eep depriva

e cages. L

n 30 min u

ns of resp

previous st

uced by no

4 or 6 h

these resp

20 h of tot

to physical

002; Novat

essed in th

sleep dep

CTH respo

d that the

r time. W

ovelty exp

ed.

gentle han

s that are

short slee

he SAM sy

e sleep de

stress res

ination. Th

ovelty expo

aekers, An

An van H

ation and

Levels com

upon term

ponses to

tudy (Beer

ovelty and

h of sleep

ponses. T

tal sleep d

l stressors

ti et al., 20

hose studie

privation o

onse (Mee

effects of

Whether

posure wil

dling proc

still detect

ep depriva

ystem whil

privation d

sponse to

hus, acute

osure, des

nnick Heyle

Hemelryck

d novelty ex

mparable

ination of

novelty ex

rling et al.

the SAM

p deprivatio

This findin

deprivation

like restra

008). Whet

es. Those

or repeated

erlo et al.

sleep dep

the beha

l be affec

edure is s

table after

ation induc

e the HPA

does not af

novelty ex

sleep dep

spite a sig

en, Gerd v

for their te

xposure

93

to non-

novelty

xposure

., 2011)

system

on with

g is in

did not

aint and

ther the

studies

d sleep

, 2002;

privation

avioural,

cted by

ufficient

novelty

ces mild

A axis is

ffect the

xposure

privation

gnificant

van den

echnical

Chapter 5

Sleep-deprived rats have normal behavioural and physiological responses to frustrative non-reward

stress

W. Beerling1, 2, J.M. Koolhaas2, A. Ahnaou1, P. Meerlo2 and

W.H.I.M. Drinkenburg1

1 Department of Neuroscience, Janssen Research & Development, a division of

Janssen Pharmaceutica N.V., Turnhoutseweg 30, 2340 Beerse, Belgium; 2 Department of Behavioural Physiology, University of Groningen, Nijenborgh 7, 9747 AG

Groningen, The Netherlands

Chapte

96

ABSTR

The outwith expbut alsoorder toand shonatural are traisuddenconsequassociafrustratithe reacadrenalaffectedacute sset-up cmonitorplasma permanactivity,operantSAM ssubsequblood pcorticosassociaan elevathe rewthe nonduring taffect thconcludsupporta delayaffect thtask or deprivatduring tsleep de

er 5

RACT

tcomes andposure to a o on the nao be truly sould involvehabitat. Thened to levely no longuence and

ated with ave non-rewctivity of the (HPA) axis

d by prior aleep deprivcombining ring of gros

corticosterent heart c body temt lever pressystem, theuently not

pressure ansterone as cated with a ated HPA a

warded grou-rewarded the last 30 he stress r

de that rewat of behavioyed HPA axhe neuroento either t

tion terminathe operant eprivation.

d the interprchallenging

ature of the stressful, nee an environerefore, theer press foer rewardesupposedl

a strong acward stress.e sympathis to rewardeacute sleepvation affecradioteleme

ss locomotorone. To doatheter. Sle

mperature ass task inde HPA axrewarded sd body temcompared treduced SAaxis activatips reachedgroups maimin of the

response toard induced

our, but thatxis recoveryndocrine anhe rewardeation. Moreotask, eithe

retation of tg situation dchallenging

eeds to conmental chae present str food or w

ed, the any experienc

ctivation of This studyco-adrenomed and non

p deprivatiocts the animetry and auor activity, o so, rats weep deprivaand plasmauced increais and indshowed a rmperature too the rewar

AM system ion as compd levels comintained an

e post-operao the reward stress sy non-rewardy. This stud

nd physiologed or non-rover, the per during rew

the outcomedo not only g situation. ntain unconallenge whictudy used awater reinfoimal faces ces loss of

the stressy aimed to dmedullary (Sn-rewardedn. The seco

mal’s behavutomated bheart rate,

were implaation causeda corticosteases in all ducing behreduced eleogether witrded animaactivation a

pared to rewmparable to

increased ant recoverrded and nstem activad, which is dy also shogical stressrewarded cerformance,ward or non

es of studiedepend onWe here h

ntrollability ch the animan operant-orcements.

absence f control. Ss systems determine iSAM) systeoperant levond aim of

viour associblood samp blood prented a smad a mild, temerone. Su

measuremhavioural aevation in th a slightlyals. The nonand reduceward. Upon

o before expHPA axis a

ry period. Pnon-rewardeation that muncontrollaows that acs response ondition, as, impulsivityn-reward, w

es combinin the sleep d

hypothesizeand unpred

mal meets inconditioningNext, wheof the exp

Such loss oand has bn a non-co

em and hypver press bethis study w

iated with tpling was ussure, bodall transmitmporary incubsequent ments, thereactivity. Anlocomotor

y stronger en-rewarded ed behavioun recovery oposure to thactivation thPrior sleep ed conditiomainly serveble and unpcute sleep in anticipa

s measuredy and motivaere not affe

ng sleep depdeprivation e that a situdictability e

n everyday g task in whn lever prepected behof control habeen descronfounded wpothalamic-pehaviour in was to assethe operantsed for cony temperat

tter togethecrease in loanticipation

efore activaimals whicactivity, heelevation incondition w

ural activity of the operahe operant hat was stilldeprivationn. Overall, ed as physpredictable,deprivationtion of the d 1.5 h afteation of the ected by pri

privation duration

uation, in elements life in its hich rats essing is havioural as been ribed as way how pituitary-rats are

ess how t task. A ntinuous ture and

er with a ocomotor n to the ating the ch were art rate, plasma

was thus but with

ant task, task but present

n did not we can

siological , caused

n did not operant

er sleep animals or acute

INTRO

Existing

(Akerst

al., 199

al., 200

depriva

neuroe

the hyp

the bas

system

rats su

affect t

2008) w

days of

axis res

2002; S

T

sleep d

sleep d

earlier

respon

betwee

behavio

respon

metabo

interpre

acute s

reviewe

uncont

should

the ani

though

ODUCTION

g literature

tedt and Fr

99; Spiege

06; Meerlo

ation of sle

endocrine s

pothalamic

sal activity

ms to challe

uggest that

he HPA ax

whereas p

f sleep res

sponse to

Sgoifo et a

The outco

deprivation

deprivation

study we

se to nove

en the ph

our induce

ses to no

olic suppo

etation. In

sleep depr

ed by Koo

rollability a

have goo

mal meets

short slee

N

e suggests

roberg, 19

el et al., 19

et al., 200

eep is ass

stress syst

c-pituitary-a

y of the st

enges (Me

t short sle

xis respons

prolonged s

striction (re

brief restra

l., 2006; N

omes and

n with expo

n duration

showed

elty expos

hysiologica

ed by this n

ovelty exp

ort of ongo

light of th

rivation aff

olhaas and

and unpre

d ecologic

s in everyd

ep depriva

Sleep

s that slee

979; von Tr

999; Chapo

08). Both co

sociated w

tem; the s

adrenal (H

ress syste

eerlo et al.

ep depriva

se to stres

sleep depr

epeated 20

aint or ines

Novati et al

the interp

osure to a

but also o

that acute

sure (Chap

al and ho

novelty exp

posure we

oing beha

hese findin

fects the r

d co-worke

edictability

cal validity

day life in

ation has b

deprivatio

ep plays a

reuer et al.

otot et al.,

ontrolled h

with increa

sympathico

PA) axis.

ems, but m

., 2008). T

ation (20 h

ssful situati

rivation (i.e

0 h of slee

scapable f

., 2008).

retation of

challengin

on the natu

e sleep de

pter 4). A

ormonal re

posure (Be

ere most

aviour rath

ngs, the n

responses

ers, a truly

(Koolhaas

and involv

its natural

been show

on and fru

an importa

., 1996; Su

2001; Hip

human and

ases in the

o-adrenome

Sleep dep

may also a

The few co

h of total s

ons (Meer

e. 48 h of t

p deprivat

foot shock

f the outco

g situation

ure of the

eprivation

close rela

esponses

eerling et a

adequate

her than t

next step w

to a truly

y stressful

s et al., 2

ve an envi

habitat (K

n not to af

ustrative n

ant role in

uchecki et

polide et al

d rodent stu

e activity

edullary (S

privation m

affect the r

ontrolled st

sleep depr

rlo et al., 2

total sleep

tion per da

stress in r

omes of s

n do not on

challengin

does not

tionship h

and the

al., 2011). C

ly interpre

the freque

would be

stressful

l situation

011). Mor

ronmental

Koolhaas e

ffect the s

non-rewar

stress reg

al., 1998;

l., 2006; S

udies show

of the two

SAM) syste

may not onl

reactivity o

tudies repo

rivation) do

002; Nova

p deprivatio

ay) alters th

rats (Meerl

studies com

nly depend

ng situation

affect the

as been r

normal o

Consequen

eted in te

ently used

to study w

situation.

should co

eover, a s

challenge

et al., 2006

tress resp

rd stress

97

gulation

Irwin et

goifo et

wed that

o major

em and

ly affect

of these

orted in

oes not

ati et al.,

on) or 8

he HPA

o et al.,

mbining

d on the

n. In an

e stress

reported

ongoing

ntly, the

erms of

d stress

whether

As was

onsist of

stressor

e, which

6). Even

onse to

Chapte

98

the ave

al., 200

depriva

and fo

animal

T

are tra

sudden

behavio

control

been d

stresso

are pa

frustrat

behavio

measu

radiote

al., 200

(Steffen

This st

other fa

applied

only a

signific

include

exposu

determ

neuroe

operan

operan

perform

attentio

both th

er 5

ersive and

08; Novati

ation affect

ot shock

towards a

Therefore,

ined to lev

nly no long

oural cons

has been

described a

or has goo

rt of every

tive non-re

oural resp

rement o

lemetry (G

07; Tang e

ns, 1969; T

tudy also

actors as s

d in this ex

mild activa

antly (Cha

ed to ensu

ure to the

ine in a

endocrine a

t lever pr

t-condition

mance, im

onal perfor

hought to

unpredict

et al., 200

ts the stre

stress sho

stress-phy

the prese

ver press f

ger reward

sequence a

n associate

as a psych

od ecologic

yday life in

eward is af

ponses we

f these

Guiol et al.,

et al., 200

Thrivikram

reduced th

sleep loss

periment.

ation of th

apter 3 and

ure that t

operant t

a non-con

and physi

ress behav

ning task

pulsivity a

rmance of

affect m

table situa

08), this do

ess respon

ould be co

ysiological

ent study u

for food o

ed (extinct

and suppo

ed with a s

hological s

cal validity

n nature.

ffected by

ere studie

responses

1992; Van

07) and an

man et al.,

he possibi

per se. Th

Earlier stu

e stress sy

d 4). A 1.5

he stress

task. Using

nfounded

ological st

viour is a

additiona

and motiv

the anima

mechanisms

tion of res

oes not ex

nse to a m

onsidered

ceiling (K

used an op

r water re

tion), the a

osedly exp

strong acti

stressor, i.

as uncon

In order

sleep dep

ed. To ac

s while re

n den Buus

n automate

2002; Roy

ility that th

herefore, g

dies in our

ystems bu

5-h recove

systems

g these m

way how

tress syste

affected by

ally allow

ation that

als. Sleep

s that are

straint or fo

xclude the

more psych

as physic

oolhaas et

perant-con

inforcemen

animal face

eriences lo

vation of t

e. frustrati

trollability

to study h

privation, p

chieve sim

educing s

se, 1994; L

ed blood s

yo et al., 2

he stress

gentle han

r lab show

ut nonethel

ery period

were bac

methods, th

w the re

ems to re

y prior ac

ws for be

will give

loss and s

e involved

oot shock

possibility

hological s

cal stresso

t al., 2006)

nditioning t

nts. When

es absenc

oss of con

the stress

ive non-re

and unpre

how the st

physiologic

multaneous

stress-conf

Leon et al.

sampling s

004; Abels

systems w

ndling sleep

ed that this

less did re

after sleep

ck to cont

he presen

eactivity o

ewarded a

ute sleep

ehavioural

more inf

stress syst

d in atten

stress (Me

y that acut

stressor. R

ors that pu

).

task in wh

lever pres

e of the ex

ntrol. Such

systems a

ward stres

edictability

tress respo

cal, hormo

and con

founding

, 2004; Gr

ystem wer

son et al.,

were activa

p deprivati

s method i

educe slee

p deprivati

trol levels

nt study ai

of the c

and non-re

deprivatio

assessm

formation

tem activat

ntional pro

eerlo et

te sleep

Restraint

ush the

ich rats

ssing is

xpected

loss of

and has

ss. This

of food

onse to

nal and

ntinuous

effects,

reene et

re used

2005) .

ated by

ion was

induced

ep times

ion was

before

imed to

classical

ewarded

on. The

ment of

on the

tion are

ocesses

(Johnso

study w

associa

METHO

Anima

At the

Horst,

experim

contain

experim

Interna

(AccuS

Univers

could b

home c

h in th

temper

light/da

animals

Food a

animals

surgery

approv

on et al., 1

was to as

ated with a

ODS

ls, housin

beginning

The Nethe

mental des

ning beddin

mental set-

ational, St

Sampler M

siteit Nijme

be housed

cages in th

he set-up

rature (21

ark regime

s were dai

access was

s at approx

y, rats had

ed all expe

1992; Brow

ssess how

an operant

ng and exp

g of the e

erlands), w

sign). The

ng and cag

-up. This s

t. Paul,

Micro, DiLa

egen, Nijm

in this set

his set-up d

prior to t

± 1°C), c

e using a 3

ly handled

s restricted

ximately 8

d full acces

erimental p

Sleep

wn et al., 2

w acute sle

task.

perimenta

xperiment,

weighing 30

animals w

ge enrichm

set-up cons

MN, USA

ab, Lund,

megen, the

-up simulta

during the

the experi

controlled

30-min dim

for weighi

d to 6 - 12

85% of thei

ss to food

protocols.

deprivatio

2012). The

eep depriv

al set-up

, 16 adult

05-340 g,

were individ

ment. The h

sisted of a

A), an a

Sweden)

e Netherla

aneously.

training se

mental da

humidity

m/rise per

ing purpos

2 g of labo

ir free-feed

prior to re

on and fru

erefore, the

vation affe

male Spr

were train

dually hous

home cage

a radiotelem

automated

and a sk

nds). With

Rats were

ession and

ay. The ro

(50 ± 10%

iod with lig

ses and wa

oratory ch

ding body

e-training. T

ustrative n

e second a

ects the an

rague-Daw

ned in the

sed in poly

e could be

metry set-u

blood s

inner box

h 7 set-ups

daily posi

were hous

oom was

%) and a

ghts on a

ater was pr

ow per da

weights. D

The local

non-rewar

aim of the

nimal’s be

wley rats (

Skinner b

ycarbonate

e positione

up (DataS

sampling

(ERG, R

s, not all a

tioned with

sed for at l

kept at c

fixed 12

t 06.00 a.

rovided ad

ay to main

During reco

ethical com

rd stress

99

present

ehaviour

(Harlan,

ox (see

e cages

d in the

ciences

system

Radboud

animals

hin their

least 24

constant

: 12 h

m. The

libitum.

tain the

overy of

mmittee

Chapte

100

Experi

Animal

reache

n=14 le

subject

cross-o

operan

subseq

same

reward

deprive

all expe

animals

experie

conditio

which 3

in para

EEG p

blood w

be test

groups

using a

showed

togethe

insuffic

As a re

control

sleep d

during

stimuli

animals

their tra

simulta

er 5

mental de

s were firs

d, the anim

eft to be re

ted to eith

over Willia

t task. One

quent norm

condition

ed conditio

ed before b

erienced t

s were ex

enced non

ons with 7

3 subsequ

allel to red

parameters

was sampl

ted simulta

of n=7 th

a balanced

d no signif

er. The da

cient quality

esult, the

+ reward

deprivation

the light

were car

s, connect

ansmitters

aneously fo

esign

st trained i

mals had t

e-trained. A

her contro

ams desig

e week lat

mal training

(control o

on of the o

became co

he reward

xposed to

n-reward.

7 days in

uent norma

duce varia

s were me

ed automa

aneously i

at had the

d design a

ficant effec

ata of a nu

y of their te

same anim

n=13; con

n + non-rew

phase, i.e

refully avo

ting them

. At least 1

or a 15-min

n the Skin

their surge

After reac

l or sleep

n, and al

ter at comp

g sessions

or sleep d

operant tas

ontrols and

ed conditio

the sam

Using thi

between a

al training s

bility amon

easured c

atically and

n the ope

eir experim

and stand

ct of testing

umber of

elemetry s

mals were

ntrol + non-

ward n=13

e. the circ

oided. The

to the aut

1 h later, te

n baseline

nner box. W

ery. Upon

hing again

p deprivatio

ll experien

parable cir

s in betwee

eprivation)

sk. Anothe

d the cont

on of the o

e conditio

is design,

and with a

sessions i

ng animals

continuous

d repeated

erant boxes

mental day

ard circad

g day there

subjects c

signals and

e not alwa

-reward n=

3. The expe

adian rest

e experime

tomated b

elemetric r

period. Th

When stab

surgery, tw

n a stable

on conditio

nced the

rcadian tim

en, the an

) but now

r week late

trol animal

operant ta

on (control

, all anim

at least 5

n between

s and beh

ly and au

ly. Becaus

s, the anim

on a diffe

dian time w

efore the d

could not

d/or blocke

ays presen

=12; sleep

erimental p

ting phase

ental day

blood samp

recordings

his baselin

le rates of

wo animal

performan

ons using

rewarded

me points a

nimals wer

w all expe

er, animals

s were sle

ask. Anothe

l or sleep

mals were

normal tra

n. Seven s

havioural,

utomatically

se only sev

mals were

erent day i

window. S

data of all g

be analyse

d blood sa

nt in all gro

deprivatio

procedures

e and pote

started w

pling syste

and blood

ne period w

f respondin

died, resu

nce, anima

a balanc

condition

and with at

re exposed

rienced th

s that were

eep-deprive

er week la

p deprivatio

exposed

aining sess

et-ups we

physiologi

y. Concom

ven anima

e divided i

n the sam

Statistical a

groups wa

ed further

ampling ca

oups resu

on + rewar

s were per

entially dis

with weigh

em and ac

d sampling

was follow

ng were

ulting in

als were

ced and

of the

t least 3

d to the

he non-

e sleep-

ed, and

ater, the

on) but

to all

sions of

re used

cal and

mitantly,

ls could

nto two

me week

analysis

as taken

due to

atheters.

lting in:

d n=14;

rformed

sturbing

ing the

ctivating

started

ed by a

6-h sle

lights-o

subseq

operan

recove

Operan

Appara

The Sk

lever, m

dispens

access

food tra

collecti

coverin

termina

Protoco

The pr

workers

addition

precisio

to fami

animals

coverin

in the fo

Also 10

Subseq

Every s

within t

eep depriv

on. These w

quent 30-m

t testing (

ry phase.

nt task

atus

kinner box

mounted o

ser. A wate

s continuou

ay entranc

on. Becau

ng metal p

ation of tra

ol

rotocol use

s (De Boe

nally given

on pellets,

iliarize the

s were pla

ng metal pl

ood tray to

0 pellets w

quently, an

session wa

their home

ation perio

were follow

min anticip

reward or

x (ERG, R

on the right

er bottle w

usly. A ligh

ce when a

use the a

late was p

ining and t

ed was ad

er et al.,

n, within th

45 mg Ro

m to the t

aced withi

lates were

o habituate

were place

nimals we

as preced

e cages in

Sleep

od or by a

wed by a 1

pation to

non-rewa

adboud U

t of the foo

was mounte

ht stimulus

pellet was

animals we

placed in f

testing.

dapted fro

1990a). O

eir home c

odent purif

taste of th

n their ho

removed

e the anima

ed on the

re trained

ed by 15

the experi

deprivatio

a non-dep

1.0-h post-

the opera

rd). This w

niversiteit

od tray wh

ed on the s

s was pos

s delivered

ere house

ront of the

m the pro

On the firs

cages, 15 h

fied diet; B

ese reinfo

ome cages

for 30 min

als to the p

lever to fa

to press

minutes d

mental set

on and fru

prived cont

-sleep depr

ant task w

was follow

Nijmegen)

hich was c

side of the

sitioned ins

d. Infrared

ed within t

e food tray

otocol desc

st day of

highly pala

Bio-Service

orcers. Dur

s in the ex

n and 20 pr

place wher

amiliarize

the lever

uring whic

t-up, follow

ustrative n

trol period

rivation rec

with subse

wed by a 1

) consisted

connected

e cage to w

side the fo

beams de

the Skinne

y and retra

cribed by

food rest

atable food

es, Uden,

ring the fo

xperimenta

recision pe

re the reinf

the anima

to obtain

ch the anim

wed by a 3

non-rewar

, both sta

covery pha

quent 30

.5-h post-

d of a retr

with a foo

which anim

ood tray to

etected foo

er box se

actable leve

de Boer a

riction, rat

d pellets (D

The Nethe

ollowing tw

al set-up a

ellets were

forcer is de

als with the

the food

mals were

0-min antic

rd stress

101

arting at

ase and

min of

operant

ractable

od pellet

mals had

o trigger

od pellet

et-up, a

er upon

and co-

ts were

Dustless

erlands)

wo days,

and the

e placed

elivered.

e lever.

pellets.

placed

cipation

Chapte

102

period

access

and the

subseq

trained

experim

with a s

with rei

a range

to reco

restricte

session

was rea

by at le

24 h

experim

min rei

lever w

describ

non-rew

Analysi

For the

determ

the nu

stable

were co

were de

er 5

during wh

s to the ret

e training

quently co

was chan

mental set-

session du

inforcemen

e of 2 to 3

over for 9-1

ed again

n followed

ached for a

east 3 sub

in the ex

mental day

nforcemen

was availa

bed as the

ward stres

is

e training d

ined. Also

mber of le

performan

ompleted,

etermined

hich the c

tracted lev

session s

mpleted s

nged every

-up. Anima

uration of 3

nts presen

32 s. Subse

13 days w

and re-tra

by 8 days

all animals

sequent tr

xperimenta

ys, rats we

nt on the V

able but n

e non-rewa

s.

days, the

the efficie

ever press

ce was rea

the numb

for the 30-

covering m

ver and foo

tarted. Tra

such a ses

y day and

als were fir

30 min. The

ted accord

equently, t

ith full acc

ained in t

on the VI-

s during thi

raining ses

al set-up

ere expose

VI-15 sche

no food w

arded cond

number o

ency was d

ses. These

ached. Fo

er of lever

-min rewar

metal plate

od tray. Af

aining was

ssion. The

every day

rst given 5

ereafter, th

ding to a va

the animal

cess to foo

two group

-15 reinforc

is period. E

ssions and

prior to

ed to 30 m

dule or 30

was deliver

dition and

f lever pre

determined

e were ca

r the expe

r presses a

rded or non

e was rem

fter 30 min

s done wit

e order in

a group w

sessions o

hey receive

ariable inte

s had thei

od. Upon re

ps on one

cement sc

Every expe

the anima

the expe

in of antic

0-min extin

red in the

is also re

esses, feed

by dividin

alculated in

rimental d

and the nu

n-rewarded

moved and

n, the leve

h 3 group

which the

was house

of continuo

ed 7 times

erval (VI) 1

r surgery a

ecovery, a

e continuo

chedule. St

erimental d

als were h

erimental

ipation wit

ction. Duri

e food tray

eferred to

der visits

ng the num

n order to

ay, the nu

umber of v

d session.

d the anim

r would co

ps of anim

e 3 group

d overnigh

ous reinfor

a 30-min

5-s sched

and were

animals we

ous reinfor

table perfo

day was pr

oused for

day. Duri

h subsequ

ing extinct

y. This is

as the fru

and rewar

mber of rew

determine

mber of tri

visits to the

mal had

ome out

als that

ps were

ht in the

rcement

session

ule with

allowed

ere food

rcement

ormance

receded

at least

ing the

uent 30-

tion, the

further

ustrative

rds was

wards by

e when

ials that

e feeder

Sleep d

Sleep d

to publ

short, w

back o

was lift

shown

4). Sle

which m

Immed

reduce

least 1

proced

the sam

Surger

After s

implant

under

mg/kg,

surgery

body te

was im

stabiliz

guided

measu

in cont

posterio

et al., 2

(Steffen

polyure

deprivatio

deprivation

lished met

whenever

r gently m

ted from i

to effectiv

ep depriva

made slee

iately follo

stress ca

10 min on

ure, anima

me experim

ry

successful

ted with a

O2-N2O-is

0.1 ml/10

y. A transm

emperature

mplanted i

ation (Gre

into the fe

rements w

tact with t

or to bregm

2007). In a

ns, 1969;

ethane; Ins

on

n started a

thods (Gra

the anima

moved. Wh

ts cage fo

ely induce

ation was

ep deprivat

owing slee

used by th

n the two

als were le

mental room

ly finishin

transmitte

oflurane a

00 g body

mitter to re

e and cort

intraperiton

ene et al.,

emoral art

were led su

he dura a

ma and an

addition, an

Thrivikram

stech Solo

Sleep

at lights-on

assi-Zucco

l showed b

en this did

or a few s

wakefulne

terminated

tion last 6

p deprivat

he sleep d

days pre

eft undistu

m.

g the Sk

r and a pe

anaesthesi

y weight)

ecord gros

ical EEG (

neally and

2007). Th

tery. Furth

ubcutaneou

at 3 mm o

nchored to

nimals rec

man et al

omon, Plym

deprivatio

using the

ni et al., 1

behavioura

d not resu

seconds. In

ess during

d after col

h and 5 m

tion, anima

eprivation

ceding the

urbed and

kinner Box

ermanent h

a. The an

was adm

s locomoto

(TL11M2-C

d attached

e blood pr

ermore, tw

usly to the

on either s

the skull w

eived a jug

., 2002).

mouth Mee

on and fru

e gentle ha

1993; Gras

al signs of

lt in visua

n a previo

the sleep

lecting the

min, which

als were le

method, a

e experim

non-depriv

x training,

heart cathe

nalgesic P

ministered

or activity,

C50-PXT,

d to the

ressure cat

wo biopote

e skull and

side latera

with screw

gular vein

The cathe

eting, USA

ustrative n

andling pro

ssi-Zuccon

sleep, it w

l activation

ous study,

deprivatio

e t= 365 m

is further

eft undistu

animals we

mental day

ved in the

animals

eter. Surge

Piritramide

subcutane

heart rate

DataScien

abdomina

theter of th

ential leads

the bare e

l to the m

ws and den

catheter fo

eter (CBAS

A) was ins

non-rewar

ocedure ac

ni et al., 20

was stroke

n of the an

this meth

n period (C

min blood s

described

urbed. In o

ere handle

. For the

eir home c

were chr

ery was pe

(dipidolor

eously at

e, blood pr

nces Intern

l wall to

he transmit

s for cortic

ends were

midline and

ntal cemen

or blood sa

S heparin

erted throu

rd stress

103

ccording

006). In

d on its

nimal, it

hod has

Chapter

sample,

as 6 h.

order to

ed for at

control

cages in

ronically

rformed

r, 0.025

start of

ressure,

national)

ensure

tter was

cal EEG

e placed

d 6 mm

nt (Tang

ampling

-coated

ugh the

Chapte

104

right ju

The ca

the skin

spiral t

blood-s

infusion

The an

Biotele

Using

Interna

telemet

and EE

signals

resulted

from th

board

using D

heart r

animals

as com

calcula

thereof

Blood

Blood w

cathete

possibl

sample

depriva

taken e

er 5

gular vein

atheter was

n in the do

o the swiv

sampling m

n of saline

imals were

emetric da

the implan

ational) be

trically mo

EG depen

s were obt

d from hor

he blood p

placed un

Dataquest

ate, blood

s in 10-s e

mpared to t

ated for the

f. Due to ar

sampling

was sampl

er. Animals

e stress-c

e volumes

ation and e

every 10 m

with the ti

s led subc

orsal region

vel and con

machine. A

+ heparin

e allowed t

ata acquis

nted trans

ehavioural

onitored. T

ndent freq

tained by

rizontal mo

pressure r

derneath e

Labpro so

pressure

epochs an

the second

e anticipati

rtefacts in

and assa

led using t

s were ha

confounding

s of 60-µ

every 30 m

min during t

p of the ca

utaneously

n of the ne

nnected ei

After surg

(10 IU/ml

to recover

sition and

mitter and

, physiolo

he transm

uency mo

monitoring

ovement of

registration

each anim

oftware (D

and body

d were av

d half hour

on period,

the EEG s

ays

he automa

abituated t

g effects o

l. Sample

min during

the anticip

atheter rea

y through

ck. The Da

ither to the

ery, anima

; 0.24 ml/h

for 9-13 da

analysis

d the Data

ogical an

mitter emitte

odulated s

g changes

f the anima

ns. The si

mal’s cage

DataScienc

temperatu

veraged an

r of the po

exposure

signals, the

ated blood

to the bloo

of it. Blood

es were t

g recovery

pation perio

aching the

a Dacron

acron butto

e infusion

als were c

h) to ensur

ays.

aquest A.R

d polysom

ed blood p

ignals. Th

s in the re

als. Heart

ignals wer

and were

ces Interna

ure data w

nd stored i

ost-sleep d

e to the ope

ese were n

sampling

od samplin

d was sam

taken eve

y of sleep

od, during

entrance o

button tha

on was con

pumps or

connected

re the cath

R.T. Syste

mnograph

pressure, b

he gross l

eceived sig

rate value

re received

e processe

ational). Lo

were samp

nto 30-min

deprivation

erant task

ot further a

system an

ng proced

pled every

ery 180 m

deprivatio

the operan

of the right

at was atta

nnected th

to the aut

to a con

eter to sta

m (DataS

ic signals

body temp

ocomotor

gnal streng

es were ca

d by an a

ed by a co

ocomotor

pled from a

n bins. De

period we

and the re

analysed.

nd the jugu

dures to m

y 10 – 180

min during

on. Sample

nt task and

t atrium.

ched to

rough a

tomated

ntinuous

ay open.

ciences

s were

perature

activity

gth that

lculated

antenna

omputer

activity,

all eight

viations

ere also

ecovery

ular vein

minimize

0 min in

g sleep

es were

d during

the 1.5

machin

stored

radioim

OH, US

the ant

Statist

To ass

measu

homog

was ini

Therefo

subject

reward

points

perform

Analyse

1.0 h p

operan

show s

post-de

operan

the rec

shown

post-de

task wi

For the

depriva

Data ar

5-h recove

ne at 4°C u

at –80°C

mmunoassa

SA) with a

ticipation p

ics

ess the eff

res ANOVA

eneity in v

tially used

ore, treatm

t factor. Sle

vs. rewa

or periods

med to de

es were do

post-sleep

t task wit

significant

eprivation

t task and

covery. Sin

and discu

eprivation

th post-op

e operant

ation or no

re presente

ery after t

until centri

until assay

ay (Mouse

sensitivity

eriod until

fect of slee

A with Gre

variance a

, the data

ment was u

eep depriv

rd) were

s as within

etermine t

one for two

deprivation

h 1.5-h po

effects, th

phase se

the post-o

nce this did

ussed for th

recovery a

erant reco

task perfo

n-reward.

ed as mea

Sleep

the operan

ifuged for

yed in dup

e/Rat Corti

of 3.0 ng/

the end of

ep deprivat

eenhouse-

assumption

of the sam

used as a

vation (slee

used as b

n-subject fa

the specif

o different

n recovery

ost-operan

e analyses

parately, a

operant ph

d not give

he analyse

and for th

very.

ormance, t

The level

an + SEM.

deprivatio

nt task. T

5 min at 3

plicate for c

icosterone

ml. Thirty-m

f the 1.5-h

tion and no

Geisser co

n was use

me animals

between-s

ep depriva

between-s

actor. Whe

fic time p

time block

y and for th

nt recovery

s were als

and for th

ase separ

a differenc

es done fo

e anticipa

t-tests wer

of significa

on and fru

The sampl

3210 rpm.

corticoster125I RIA K

minute ave

post-opera

on-reward

orrection e

ed. Even t

s was not a

subjects fac

tion vs. co

ubject fac

en approp

oints at w

ks: the peri

he anticipa

y. If these

so done fo

he anticipa

ately, in or

ce in signif

or the perio

tion period

re used to

ance was a

ustrative n

es were s

Subseque

rone with a

Kit, MP Bio

erages wer

ant recove

on all vari

psilon (ε) f

hough a c

always pre

ctor rather

ontrol) and

tors and t

priate, post

which the

iod of slee

ation period

e ANOVA

or the slee

ation with

rder to che

ficance, th

od of sleep

d, exposur

assess th

accepted a

non-rewar

stored ins

ently, plasm

a double a

omedicals,

re calculat

ery period.

iables, a re

for violatio

cross-over

sent in all

r than as a

non-rewar

the differe

t-hoc t-tes

groups d

p deprivat

d, exposur

analyses

p deprivat

exposure

eck for an e

e results a

p deprivati

re to the

he effect o

at p-values

rd stress

105

side the

ma was

antibody

, Solon,

ed from

epeated

n of the

design

groups.

a within-

rd (non-

ent time

ts were

differed.

ion with

e to the

did not

ion and

to the

effect in

are only

ion with

operant

of sleep

s <0.05.

Chapte

106

RESUL

Dynam

sleep d

Sleep d

Data o

corticos

conditio

(panels

ANOVA

(F13,624=

temper

ε=0.6,

overall

heart r

blood p

reward

respect

depriva

sleep d

time p

compa

showed

the con

increas

plasma

corticos

lower le

as com

recove

the sle

higher

er 5

LTS

mics of the

deprivatio

deprivation

on locomo

sterone re

on and the

s A-E, resp

A showed

=10.4, ε=0

rature (F13

p=0.006).

sleep dep

rate (F1,48=

pressure a

effect w

tively). Po

ation perio

deprivation

oints duri

red to the

d a signific

ntrol + rew

sed by sle

a corticoste

sterone lev

evels were

mpared to t

ry of sleep

ep depriva

plasma co

e behavio

on with su

n and conse

otor activit

esponses d

e 1.0-h po

pectively).

a significa

0.5, p<0.0

3,624=2.0, ε

A signific

privation eff

=4.1, p=0.0

and plasma

was also

ost-hoc ana

d that rea

n procedur

ng the la

e control +

cant increa

ward group

eep depriv

erone, at b

vels as co

e reached

the sleep

p deprivatio

ation perio

orticosteron

ural, phys

bsequent

ecutive rec

ty, heart

during 6-h

ost-depriva

ant time*sle

001), blood

ε=0.5, p=0

cant effect

fect was fo

05) and p

a corticost

found (F

alysis sho

ached cont

re. Heart r

st 3-h of

+ reward g

ase for the

p. In contr

vation duri

baseline, th

mpared to

again duri

deprivation

on as comp

od, the slee

ne levels a

siological

frustrativ

covery

rate, bloo

sleep de

ation recov

eep depriv

d pressure

0.009) an

t of time w

ound for lo

plasma cor

erone, a s

13,624=2.6,

wed incre

trol levels

rate reache

the sleep

group. For

sleep-dep

rast, body

ing most

he control +

o the sleep

ng the last

n + reward

pared to al

ep depriva

s compare

and horm

ve non-rew

od pressur

privation o

very phase

vation inter

e (F13,624=5

d plasma

was found

comotor ac

rticosteron

significant

ε=0.6, p

eased activ

immediate

ed significa

p deprivat

blood pre

prived + rew

temperatu

of the sle

+ reward g

-deprived

t 5 min of t

d group an

ll groups. O

ation + rew

ed to all gro

monal resp

ward stres

re, body

or the non

e are illust

raction for

5.6, ε=0.6

corticoste

for all m

ctivity (F1,4

e (F1,48=8

time*sleep

p=0.01; F1

vity levels

ely upon t

antly highe

tion period

essure, on

ward grou

ure levels

eep depriv

group had

+ non-rew

the sleep d

nd during t

Only during

ward group

oups.

ponses to

s

temperatu

n-deprived

trated in F

locomotor

6, p<0.001

erone (F4,

measureme

48=84.8, p<

.9, p=0.00

p deprivatio

1,48=6.0, p

during the

termination

er levels a

d and ma

ly one tim

p as comp

were sign

vation perio

significant

ward group

deprivation

the first 30

g the first 5

p had sign

o 6 h of

ure and

control

Figure 1

r activity

), body

192=3.9,

ents. An

<0.001),

05). For

on*non-

p=0.018

e sleep

n of the

at some

ainly as

me point

pared to

ificantly

od. For

ly lower

. These

n period

0 min of

5 min of

ificantly

Upon t

levels

deprive

other g

Frustra

Data o

corticos

of the

1.5-h

respect

ANOVA

(F4,192=

(F4,192=

signific

effect w

signific

depriva

rate, a

p=0.04

reward

To acc

reward

recove

body te

anticipa

recove

locomo

p=0<0.

temper

all resp

termination

within 1 h

ed + rewa

roups.

ative non-re

on the loco

sterone re

sleep dep

post-opera

tively).

A showed

=3.6, ε=0.4

=9.4, ε=0.5

ant effect

was found

ant non-re

ation only a

significan

5) and fo

interaction

ount for th

group, the

ry period w

emperature

ation perio

ry period.

otor activity

001), delt

rature (F4,1

ponses. A

n of the sle

h. The on

rd group,

eward stre

omotor ac

sponses d

rivation, a

ant recov

a signifi

4, p=0.046)

5, p<0.001

of time w

d for plasm

eward effe

affected he

nt time*sle

or plasma

n was foun

he unrecov

e differenc

was calcula

e. These a

od and ex

ANOVA s

y (F4,192=3

ta blood

92=4.9, ε=

A significan

Sleep

eep depriv

ly exempt

which sta

ss and con

tivity, hea

during the

nd during

ery phase

cant time

), heart rat

1) and bod

was found

ma cortico

ct for bod

eart rate a

eep depriv

corticoste

nd (F4,192=3

vered body

ce as comp

ated for lo

are shown

xposure to

showed a s

3.6, ε=0.4,

pressure

0.5, p=0.0

nt time*sle

deprivatio

vation proc

tion was t

ayed signif

nsecutive r

rt rate, blo

anticipatio

exposure

e are illu

*non-rewa

te (F4,192=1

dy temper

for all m

osterone (

y tempera

and plasma

vation inter

erone a si

3.3, ε=0.9,

y temperatu

pared to th

ocomotor a

n in Figure

o the oper

significant

p=0.046),

(F4,192=9.4

09). A sign

eep depriva

on and fru

cedure, all

the body

ficantly ele

recovery

ood pressu

n period s

to the op

ustrated in

ard interac

10.6, ε=0.7

rature (F4,1

easureme

F1,48=26.6

ature (F1,48

a corticost

raction wa

gnificant t

p=0.016).

ure respon

he last 30 m

activity, hea

e 2 (panels

rant task a

time*non-

, delta hea

4, ε=0.5,

nificant tim

ation inter

ustrative n

responses

temperatu

evated as

ure, body

starting 1 h

erant task

n Figure

ction for l

7, p<0.001

192=4.9, ε=

nts. An ov

, p<0.001

8=2.3, p=0

terone resp

as found (

time*sleep

nse for the

min of the

art rate, blo

s A-D, res

and the 1

-reward int

art rate (F

p<0.001)

me effect w

raction wa

non-rewar

s reached

re for the

compared

temperatu

h after term

k with subs

1 (panel

ocomotor

1), blood p

=0.5, p=0.0

verall non

) and a c

.066). Prio

ponses. Fo

(F4,192=2.8,

deprivatio

e sleep-dep

sleep dep

ood pressu

spectively)

.5-h post-

teraction fo

F4,192=10.6

and delta

was also fo

s found fo

rd stress

107

control

e sleep-

d to the

ure and

mination

sequent

ls A-E,

activity

pressure

009). A

-reward

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or sleep

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, ε=0.5,

on*non-

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ure and

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, ε=0.7,

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ound for

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Chapte

108

heart ra

found f

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reward

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temper

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er 5

ate (F4,192=

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otor activity

ed animals

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ation + rew

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te activity

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group. T

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ody temper

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y temperat

erone leve

reased ch

compared

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y was obs

s. Furtherm

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observed

her absol

ward group

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els, plasma

vation + no

.

0 min of th

both non-r

body te

ward grou

ward group

. During th

levels we

non-rewa

ted for the

n-reward g

The last 30

rone levels

groups.

7, p=0.045

rature (F1,4

ant task, po

ure for the

els for the

ange in b

to the con

erant task,

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th rewarde

as compa

ute body

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er locomot

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he post-op

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mperature

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re reache

ard groups

ese 30 m

roup had a

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5) and a si

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ost-hoc an

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e control +

lood press

ntrol + rewa

a tendenc

the non-re

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ed groups

ared to th

temperatu

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tor activity

erone leve

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perant reco

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mpared to

er plasma

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. This was

min only.

a higher d

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ched for th

ignificant s

0.031).

nalysis of t

privation +

+ non-rewa

sure for th

ard group w

y for a dec

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heart rate f

was found

e control

ure levels

ll other gr

y, heart rat

ls were inc

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gnificantly

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st-operant t

sleep dep

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During the

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ard group

he sleep d

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crease in a

animals as

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+ reward

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oups. Whe

e, blood p

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evels as c

od, the del

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decrease

rol groups

erone level

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rivation +

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e same p

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ecovery pe

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. For delta

eprivation

.

absolute an

compared

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ta heart ra

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Chapte

112

DISCU

The pr

depriva

stress

Second

affected

I

increas

anticipa

which i

1990a)

non-rew

reduce

temper

as com

Non-re

elevate

associa

numbe

of motiv

with the

and Re

studies

et al., 1

al., 198

non-rew

when lo

al., 197

workers

increas

system

Boer e

er 5

SSION

resent stud

ation affec

systems

dly, this s

d by acute

In anticipa

sed for all

ation activa

s in accord

). The resp

ward effec

d elevatio

rature leve

mpared to t

ward was

ed HPA a

ated with

r of trials i

vation. The

e view that

eisine, 1984

s that foun

1990a) and

84; De Boe

ward is als

osing beha

76; Hart an

s further

sed during

m activation

t al., 1990

dy aimed t

ts the rea

to reward

tudy aime

e sleep dep

ation of th

groups. Th

ated the SA

dance with

ponses furt

ct became

n in gross

ls together

he reward

thus ass

axis activa

reduced l

initiated, le

e reduced

t SAM sys

4; Leal-Ce

d a reduce

d higher H

er et al., 1

so in line

avioural co

nd Coover,

showed t

non-rewa

n and indiv

0a). In the

to determi

activity of t

ded and n

ed to asse

privation.

he operant

his was no

AM system

h observat

ther increa

e visible. A

s locomoto

r with a slig

ed animals

sociated w

ation as

ocomotor

ever presse

SAM syst

stem activa

erro et al., 2

ed elevatio

HPA axis a

990a). Th

with other

ontrol (Coo

1982; Co

that adren

ard. They a

vidual diffe

present st

ine in a no

the classic

non-reward

ess how b

t lever pre

ot affected

m and HPA

ions of de

ased during

Animals w

or activity,

ghtly strong

s and this w

with a redu

compared

activity le

es and fee

em activat

ation is ass

2003). The

on in norad

activation (

e increase

r studies s

over et al.,

e et al., 19

nalin disso

also showe

erences in

tudy, some

on-confoun

cal neuroe

ded opera

behaviour

ess task,

by prior s

A axis and

Boer and

g the opera

which were

heart rate

ger elevati

was not af

uced SAM

to rewa

evels that

eder visits,

tion in the

sociated w

e findings a

drenalin du

Boulos an

ed HPA ax

showing st

1971a; Co

983; Osbor

ociated fro

ed a close

n behaviou

e individua

nded way

endocrine

ant lever

during the

all physio

leep depriv

increased

co-worker

ant task fo

e not rew

e, blood pr

ion in plasm

ffected by

M system

rd. Also,

were refle

reflecting

non-rewar

ith physica

are also in

uring non-

d Terman

xis activatio

tronger HP

oover et al

rne, 1986)

om noradr

e associati

ural lever p

al differenc

how acut

and physi

press beh

e operant

ological me

vation. The

the activit

rs (De Boe

r all group

warded sho

ressure an

ma cortico

sleep depr

activation

non-rewa

ected in r

an appare

rd groups is

al activity (A

line with p

reward (D

, 1980; Co

on in resp

PA axis ac

., 1971b; D

. De Boer

renalin, an

on betwee

press activ

ces in beha

e sleep

ological

haviour.

task is

easures

erefore,

ty levels

er et al.,

s and a

owed a

nd body

osterone

rivation.

but an

rd was

reduced

ent loss

s in line

Axelrod

previous

De Boer

oover et

onse to

ctivation

Davis et

and co-

nd was

en SAM

vity (De

avioural

lever p

physiol

T

press t

study

activati

activity

to leve

decrea

decrea

to the

mainta

that wa

not affe

O

Activat

stress

control

al., 198

also ob

reward

crucial

show th

charact

system

require

co-wor

contain

hypothe

behavio

study, t

the beh

showed

press activ

ogical and

The recove

ask, with p

shows no

on during

and blood

els compa

sed but m

se. Where

levels be

ined an inc

as still pres

ect the reco

Our obser

ion of the

as this act

lable situa

84; De Boe

bserved in

. In this r

for mobili

hat the neu

teristics as

m activation

ements for

kers, a s

ning unco

esized tha

oural activ

the plasma

havioural a

d similar t

ity were fo

d hormonal

ery of the p

prior sleep

o differenc

the last 30

d pressure

arable to

maintained

eas the rew

efore exp

creased H

sent durin

overy of th

rvations ar

SAM and

tivation so

tions (Sch

er et al., 19

our study

rewarded c

zation of e

uroendocri

s the beha

n during t

normal on

situation s

ontrollability

at a truly

vity respo

a corticoste

activity resp

temporal c

Sleep

ound but t

l response

physiologic

deprivatio

ce betwee

0 min of th

responses

before ex

higher leve

warded gro

osure to

PA axis ac

g the last

he respons

re in agree

d HPA axi

metimes a

uurman, 1

990a; Arnh

y, with activ

condition,

energy ne

ine and ph

avioural ac

the reward

ngoing beh

hould be

y and un

y stressfu

nse and

erone resp

ponse duri

characteris

deprivatio

these were

s or with p

cal respons

on, has not

en reward

he post-op

s all decre

xposure to

els for all

oups reach

the opera

ctivation du

30 min of

es after re

ement wit

is system

also occurs

980; Brons

hold et al.,

vation of th

the stress

eded to co

hysiologica

ctivity resp

ded condit

havioural a

considere

npredictab

l situation

the physio

ponse had

ng non-rew

stics as the

on and fru

e not corre

prior sleep

ses after e

t previously

d and non

perant reco

eased durin

o the ope

groups an

hed cortico

ant task,

uring the p

f recovery.

ward and

h our view

alone is n

s in respon

son and D

2009; Buw

he SAM sy

s system

omplete th

l stress res

ponse. Th

tion is a

activity. As

ed a truly

ility (Koo

n causes

ological/ho

different te

ward, whe

e behaviou

ustrative n

elated with

deprivation

exposure to

y been stu

n-reward

overy perio

ng the 1.5-

rant task.

d body tem

osterone le

the non-r

post-operan

Prior slee

non-rewar

w of the c

not enoug

nse to high

esjardins,

walda et al

ystem and

activation

he task. In

sponse ha

is suggest

reflection

reviewed

y stressful

lhaas et

dissociati

ormonal re

emporal ch

reas SAM

ural activit

non-rewar

h the beha

n.

o an opera

died. The

on SAM

od. The loc

-h recovery

Heart ra

mperature

evels com

rewarded

nt recovery

ep depriva

d.

concept of

gh to chara

hly reward

1982; Shir

., 2012). T

d HPA axis

is though

ndeed, our

s similar te

ts that the

of the me

by Koolha

l situation

al., 2011

ion betwe

esponses.

harecterist

system ac

ty respons

rd stress

113

avioural,

ant lever

present

system

comotor

y period

ate also

did not

parable

groups

y period

tion did

stress.

acterize

ing and

raishi et

This was

s during

ht to be

r results

emporal

e stress

etabolic

aas and

, when

1). We

een the

In our

ics than

ctivation

se. This

Chapte

114

was al

temper

recove

behavio

under r

in SAM

differen

betwee

recove

display

referred

This is

SAM sy

one, th

et al., 2

T

that ac

and tri

initiated

animals

the rew

was no

reduce

acute s

the ope

mecha

et al.,

behavio

U

heart ra

Wollnik

Therefo

Other c

er 5

lso observ

rature resp

ry and the

oural resp

rewarded a

M system a

nces in be

en the rew

ry period w

yed low be

d to as fru

in line wit

ystem resp

at was not

2000; Fish

The opera

cute sleep

als initiate

d trials co

s. This ind

warded an

ot affected

d motivatio

sleep depr

erant task.

nisms that

2012). W

oural meas

Under non

ate, blood

k, 1982; De

ore, the a

confoundin

ved during

ponse that

refore also

onse. Whe

and non-re

activation b

ehavioural

warded and

was not d

havioural a

ustrative n

th studies

ponse afte

t due to dif

et al., 200

nt task als

deprivation

ed under r

orresponds

icates that

imals. Also

d by slee

on but this

rivation did

. Sleep los

t are involv

We suggest

sures in th

n-deprived

pressure,

e Boer and

nimals we

ng factors

g the reco

t showed

o had differ

en compa

ewarded c

between re

activity. In

d non-rewa

ue to a di

activity. Th

on-reward

showing a

r an uncon

fferences in

05; Arnhold

so allowed

n did not a

rewarded

s to the n

t acute sle

o the moti

ep depriva

s was not a

d not affec

ss and stre

ved in atte

t that mor

e operant

control co

body temp

d van der

ere most li

may howe

overy of t

a delayed

rent tempo

ring the S

conditions,

ewarded a

n contrast,

arded con

ifference in

herefore, w

d stress, ca

a delayed

ntrollable s

n behaviou

d et al., 200

for behav

affect the n

and non-r

number of

eep depriva

vation and

ation. The

affected by

ct the atten

ess system

entional pro

re prolong

tasked use

onditions,

perature an

Gugten, 1

kely not a

ever have

the respon

d recovery

oral charac

SAM syste

the data s

nd non-rew

the plasm

dition at t

n behaviou

we can con

aused a d

recovery o

situation as

ural activity

09; Koolha

vioural obs

number of

rewarded

f rewards

ation did no

d impulsivi

non-rewa

y a prior s

ntional per

m activation

ocesses (J

ed sleep

ed in this s

the anima

nd plasma

987) toge

affected by

been pre

nses, exce

y for all g

cteristics as

m and HP

suggests t

warded co

ma corticos

he end of

ural activit

nclude that

delayed HP

of the cort

s compared

y (Schuurm

aas et al., 2

ervations.

lever pres

conditions

received

ot affect th

ity of the r

arded anim

leep depriv

rformance

n are both

Johnson et

deprivatio

study.

als showed

corticoste

ther with lo

y the sam

esent, as u

ept for th

groups dur

s compare

PA axis ac

hat the dif

onditions is

sterone dif

f the post-

ty as both

t non-rewa

PA axis re

ticosterone

d to a cont

man, 1980;

2011).

The result

sses, feede

s. The num

by the re

he perform

rewarded a

mals did s

vation. The

of the ani

h thought t

t al., 1992

n may aff

d normal le

erone (Butt

ow activity

pling proc

unexpected

e body

ring the

d to the

ctivation

fference

s due to

fference

operant

groups

ard, also

ecovery.

e and/or

trollable

; Garcia

ts show

er visits

mber of

ewarded

ance of

animals

show a

erefore,

imals in

to affect

; Brown

fect the

evels of

ner and

y levels.

cedures.

d group

differen

effect w

expose

differen

T

much a

experim

confirm

activity

pressu

increas

metabo

depriva

2003).

depriva

increas

Sgoifo

above

and W

mildly.

be in a

state w

though

increas

1979;

conseq

that th

conseq

the end

minimiz

experim

(Meerlo

agitated

nces were

was observ

ed to the o

nces and o

To minimiz

as possible

ment. The

med by our

and body

re and he

ses are ind

olic suppor

ation (Axe

Also plasm

ation which

ses in plas

et al., 200

those reac

ollnik, 198

Despite th

n agitated

was reflect

published

sed aggres

Gessa et

quence of

is is the

quence of s

d of the sle

ze confou

ment, we a

o et al., 2

d state a

observed

ved during

operant tas

other expla

ze stress c

e, the gen

efficacy of

r previous

temperatu

eart rate w

dicative of

rt for the i

lrod and R

ma cortico

h is in ac

sma cortico

06; Meerlo

ched durin

82). Theref

his mild ac

state towa

ed in the

d results

ssiveness

al., 1995

sleep loss

result of

stress indu

eep depriva

nding effe

applied an

002; Sgoif

nymore af

Sleep

. Baseline

g the sleep

sk. Individu

anations co

confoundin

tle handlin

f 6-h sleep

study (Cha

ure through

were only

f SAM sys

ncreased

Reisine, 1

osterone le

ccordance

osterone d

et al., 200

ng the activ

fore, acute

ctivation of

ards the e

animals re

do not m

have been

; Tartar e

s per se o

accumula

uced by th

ation sessi

ects of thi

n undisturb

fo et al., 2

fter this 1

deprivatio

difference

p deprivati

ual variatio

ould also no

ng effects o

ng sleep de

p deprivatio

apter 4). S

hout the sl

increased

stem activa

activity an

984; John

evels were

with othe

during slee

08). For all

ve phase

e sleep de

the stress

nd of the s

eacting mo

mention ag

n reported

et al., 200

r of the sl

ting sleep

e procedu

on. Future

s agitated

bed recove

2006). Th

1-h recove

on and fru

es were fo

on period

on was no

ot be found

of the slee

eprivation

on by our g

Sleep depr

eep depriv

d at some

ation that

nd wakeful

nson et a

e only sligh

er rodent

ep depriva

responses

under hom

eprivation a

s systems,

sleep depr

ore aggres

itation spe

d after slee

08). It is u

eep depriv

p debt and

re, as agit

e studies ar

d state as

ery period

e animals

ery of slee

ustrative n

und and a

while the

ot the caus

d.

ep deprivat

method w

gentle han

rivation enh

vation perio

e time poin

may be n

ness asso

l., 1992; L

htly affecte

studies sh

tion (Such

s, levels w

me cage co

affected th

some ani

ivation per

ssive to ou

ecifically,

ep depriva

unknown w

vation met

d tirednes

ation only

re needed

s much as

following

appeared

ep depriva

non-rewar

also a non

rats were

se of these

tion proce

was applied

dling meth

hances loc

od wherea

nts. These

needed to

ociated wit

Leal-Cerro

ed by sho

howing m

hecki et al

were not inc

onditions (

he stress s

mals appe

riod. This a

ur handling

hyperactiv

ation (Hicks

whether th

thod. We s

ss, rather

occurred t

to confirm

s possible

sleep dep

d not to b

ation perio

rd stress

115

-reward

not yet

e group

dure as

d in this

hod was

comotor

as blood

e minor

provide

th sleep

o et al.,

rt sleep

oderate

., 1998;

creased

(Buttner

systems

eared to

agitated

g. Even

vity and

s et al.,

his is a

suggest

than a

towards

m this To

in our

privation

e in an

od. We

Chapte

116

previou

presen

O

mainly

uncont

also sh

physiol

reward

termina

depriva

restrain

2008).

unpred

found i

be affe

perform

during

ACKNO

The au

Heidi H

er 5

usly showe

t after 1.5

Overall, w

served as

rollable an

hows that

ogical stre

ed or non

ation. This

ation (20 h

nt stress a

Despite

ictability a

n our stud

ected by

mance, imp

reward or

OWLEDGE

uthors wou

Huysmans

ed that 6 h

h recovery

we can con

s physiolog

nd unpredi

acute sle

ess respo

n-rewarded

s finding i

h) does no

and inesca

the use

and uncon

y. Whethe

prolonged

pulsivity an

non-rewar

EMENTS

uld like to

for their te

h of sleep d

y of sleep d

nclude tha

gical supp

ctable, ca

eep depriv

nse in an

d condition

s in agre

t affect the

pable foot

of a na

ntrollability,

r the stres

d sleep d

nd motivati

rd, were no

thank Lee

echnical as

deprivation

deprivation

t reward i

ort of beh

used a de

vation did

ticipation

n, as mea

eement wit

e HPA axis

tstock stre

atural and

, still no e

ss response

deprivation

on of the a

ot affected

en Raeym

sistance.

n induced

n (Chapter

nduced st

aviour, bu

elayed HPA

not affec

of the ope

asured 1.5

th studies

s respons

ss (Meerlo

d psycholo

effect of p

es to frustr

n remains

animals du

by prior ac

maekers, G

a sleep de

4).

tress syste

ut that non

A axis rec

ct the neu

erant task

5 h after

showing

se to phys

o et al., 20

ogical str

prior sleep

rative non-

to be s

uring the op

cute sleep

Gerd van d

eficit that w

em activati

n-reward, w

covery. Thi

uroendocri

k or to eit

sleep dep

that shor

sical stress

002; Novat

ressor con

p deprivatio

-reward str

studied. A

perant task

deprivatio

den Kieboo

was still

ion that

which is

is study

ne and

ther the

privation

rt sleep

sors like

ti et al.,

ntaining

on was

ress will

lso the

k, either

on.

om and

Chapter 6

Attentional and physiological aspects measured in the 5-choice serial reaction time task are unaffected by

acute sleep deprivation in rats

W. Beerling1,2, M.C. Schippers2, J.M. Koolhaas2, D. Pemberton1, A. Ahnaou1,

P. Meerlo2 and W.H.I.M. Drinkenburg1

1 Department of Neuroscience, Janssen Research & Development, a division of

Janssen Pharmaceutica N.V., Turnhoutseweg 30, 2340 Beerse, Belgium; 2 Department of Behavioural Physiology, University of Groningen, Nijenborgh 7, 9747 AG

Groningen, The Netherlands

Chapte

118

ABSTR

Controll

selectiv

investig

attentio

CSRTT

holes in

compon

behavio

body te

using a

perform

points, o

sleep d

during s

was ind

Non-Ra

controls

termina

REM sl

was sig

minutes

for the

indicate

that are

affect t

correct

termina

Perseve

caused

respons

acute g

behavio

er 6

RACT

led human

ve attention

ate, in a n

nal process

, rats detec

n order to

nent proces

oural contro

emperature

a small im

mance and

on the base

deprivation

sleep depri

duced with

apid Eye M

s. The delta

tion of the

eep duratio

gnificantly i

s after term

sleep-depr

es that 6-h

e still detect

the respons

response

tion. Also

erative resp

by a chan

ses as com

entle handl

oural contro

and roden

and can

non-confoun

ses in the 5

ct and resp

get a food

sses of att

ol. Besides

and polys

mplantable t

telemetric

eline day, o

and after 2

ivation a si

a concomit

Movement (

a power duri

sleep dep

on reached

ncreased w

mination of t

rived anima

sleep depr

table 30 m

se accurac

latency in

body tem

ponses were

nge in the

mpared to b

ing sleep d

l in the 5-C

nt studies s

lead to im

nded way,

5-choice se

pond to a 0

d reward. T

tention, suc

assessing

somnograph

transmitter.

measureme

n the exper

24 h recov

gnificant in

tant lack of

(NREM) sle

ing NREM s

privation pro

levels at o

with a con

the 5-CSRT

als with a

rivation indu

in after term

cy, correct

the 5-CS

mperature

e slightly inc

control anim

baseline, du

eprivation d

SRTT.

show that s

pairments

how acute

erial reactio

0.5-slight s

The 5-CSRT

ch as sele

these atten

hic parame

After trai

ents were

rimental day

very of slee

ncrease in l

f Rapid Eye

eep occurre

sleep was u

ocedure, lo

r below tho

comitant de

TT, NREM

decreased

uced a sign

mination of

responses

RTT as m

and locom

creased by

mals that d

ue to unkno

does not aff

sleep depriv

in attention

e, 6-h sleep

on time task

timulus pre

TT allows

ective atten

ntional aspe

eters were

ning the a

assessed a

y starting 1.

ep deprivat

locomotor a

e Movemen

ence as co

unaffected d

ocomotor ac

ose of the c

ecrease in

and REM s

delta pow

nificant slee

the 5-CSR

s, omission

measured 1

motor activ

sleep depr

decreased t

own reason

fect sustain

vation redu

n tasks. Th

p deprivatio

k (5-CSRTT

esented ran

close obse

tion, susta

ects, gross

measured

animals to

at compara

.5 h after th

tion. The re

activity and

nt (REM) sl

ompared to

during sleep

ctivity, bod

controls. NR

wakefulne

sleep durat

wer during

ep loss, wh

RTT. Sleep

s, prematu

1.5 h after

vity levels

rivation. Thi

their amou

n. We there

ned and sele

uces sustain

his study a

on affects

T) in rats. I

ndomly in o

ervation of

ined attent

locomotor

by radiote

criteria, 5

able circad

e terminatio

esults show

d body tem

eep and al

o the non-d

p deprivatio

y temperat

REM sleep

ess duration

ion were in

NREM slee

hich caused

deprivation

ure respons

r sleep dep

were una

s effect wa

nt of perse

efore conclu

ective atten

ned and

aimed to

different

n the 5-

one of 5

different

tion and

activity,

elemetry

-CSRTT

ian time

on of the

wed that

perature

most no

deprived

on. Upon

ture and

duration

n. Thirty

ncreased

ep. This

d effects

n did not

ses and

privation

affected.

s mainly

everative

ude that

ntion and

INTRO

Today’s

subject

hours)

shortag

tasks o

attentio

showed

tasks th

et al., 2

sustain

been m

The fa

differen

underly

stress

physica

Sapols

1998;

process

Durme

prefron

Therefo

observe

E

the str

frustrat

studies

physica

2002; N

depriva

operan

ODUCTION

s society

ts as a res

and in pa

ge, most p

or stressfu

on are am

d that a si

hat require

2002; Van

ned attentio

made to un

ct that att

nt varieties

ying mecha

systems.

al activity b

ky, 1995;

McEwen

ses involv

r and Ding

ntal cortex

ore, stress

ed after sle

Earlier stu

ress respo

tive non-re

s showing

al stressor

Novati et a

ation does

t task that

N

is full of

sult of lifest

atients wit

people are

ul challeng

ong the fi

ngle night

e attention

Dongen e

onal dema

nravel the u

tention is

s of atten

anisms. O

Stress ho

but also af

Quirarte e

and See

ed in atten

ges, 2005)

and to re

s system

eep depriv

dies in ou

onses to e

eward stre

no effect

rs like res

al., 2008). M

not affect

t was used

acute an

tyle (e.g. s

h sleep, m

e daily face

ges. In hu

rst conseq

of sleep l

to auditor

et al., 2003

and (Drum

underlying

not a unit

ntional pro

ne of the h

ormones d

ffect brain

et al., 1997

eman, 199

ntion main

. Interestin

sult in def

activation

vation.

r lab show

ecologicall

ess (Chapt

of acute

straint and

Moreover,

the anima

d to induce

nd chronic

shift work,

medical or

ed with co

umans, re

quences o

oss leads

ry or visua

3), but also

mond et a

mechanis

tary pheno

ocesses m

hypothesiz

do not on

functionin

7; Arnsten

99; McEw

nly rely on

ng is that c

ficits in pre

n may be

wed that ac

y valid ch

ter 4 and

sleep dep

inescapa

studies in

l’s motivat

e frustrative

Sleep dep

c sleep dis

(social) jet

r psychiatr

omplex situ

eductions

of sleep lo

to impairm

l stimuli (J

o to stimuli

al., 2001).

sms, these

omenon bu

makes it

zed mecha

ly support

ng, cognitio

n, 1998; Ar

wen, 1999

the prefro

chronic stre

efrontal co

involved

cute sleep

hallenges

5). This is

privation o

ble foot s

our lab al

ion, impuls

e non-rewa

privation a

sturbance,

t lag and p

ric disorde

uations, e.

in sustain

ss and sle

ments in su

Jewett et a

with a hig

While ma

e are still p

ut more a

complex t

anisms is in

t metaboli

on and mo

rnsten and

a; McEwe

ontal corte

ess has sh

ortex -med

in the a

deprivatio

like novel

s in accor

on the stre

hock stres

lso showed

sivity and p

ard stress

and the 5-

, both in

prolonged w

rs. Despite

.g. neuroco

ed and s

eepiness.

ustained a

al., 1999; J

gher select

ny attemp

poorly unde

term for

to determ

nvolvemen

c process

ood (McEw

d Goldman

en, 1999b

x (Norton

hown to af

diated beha

attentional

on does no

lty exposu

rdance wit

ess respon

ss (Meerlo

d that acut

performanc

(Chapter

CSRTT

119

healthy

working

e sleep

ognitive

elective

Studies

attention

Johnsen

tive and

ts have

erstood.

several

ine the

nt of the

ses and

wen and

n-Rakic,

b). The

n, 1970;

ffect the

aviours.

deficits

ot affect

ure and

th other

nses to

o et al.,

te sleep

ce in an

5). This

Chapte

120

was su

mecha

and Ho

presen

attentio

sleep d

a more

differen

attentio

resultin

rely on

attentio

and co

aspects

effects

F

The 5-C

presen

animal

respon

attentio

prior to

and ter

for imp

measu

location

across

impulsi

psycho

these t

results

human

attentio

er 6

rprising as

nisms of a

orne, 1999

t study aim

onal and p

deprivation

e complex

nt compon

on and be

ng from sle

n the prefr

on to releva

ognitive pe

s of exec

on the und

For this pu

CSRTT is

ted random

must mai

d correctl

on in both

o the prese

rminate the

pulsivity me

rements th

n, duration

trials, ena

vity. The

omotor vigi

tests are o

of disturb

situation.

on are ext

s studies s

attention (N

9; Durmer

med to stu

physiologic

method a

x and spe

nent proce

havioural c

eep loss re

rontal cort

ant cues (N

erseveratio

utive func

derlying m

urpose, the

a task in

mly in one

intain atte

ly. Accura

the tempo

entation of

e trial, the

easuremen

hat also gi

n, and timin

abling asse

5-CSRTT

lance task

often used

bed attent

An addit

tensively s

uggest tha

Norton, 197

and Dinge

udy in more

al respons

s in our pr

cified ope

sses of at

control. Pr

eflect a dys

tex (Norto

Norton, 19

on (Horne,

ction. This

echanisms

e 5-choice

which rats

of 5 holes

ntion to th

ate respon

oral and sp

the stimu

task also p

nt. The 5-C

ve more in

ng (pre-stim

essments

is compa

k in human

in combin

tional perf

tional adva

studied on

at sleep de

70; Horne,

es, 2005;

e detail wh

ses in a ne

revious stu

rant task

ttention, s

revious stu

sregulation

n, 1970; D

70), flexibl

1988; W

indicates

s of attentio

serial rea

s have to d

s in order

he 5 holes

nding thus

patial dom

lus (prema

places dem

CSRTT als

nformation

mulus dela

of sustain

arable to t

s (Robbins

nation with

formance

antage is

n the basis

privation h

, 1988; Wi

Cordova e

hether acu

eurocognit

dies (Chap

that allow

uch as se

udies sugg

of behavio

Durmer an

e thinking

immer et

that slee

on.

action time

detect and

to get a fo

s in order

s requires

mains. In ad

ature respo

mands on

so allows fo

on the be

ay) of the v

ed and se

he continu

s, 2002; B

h sleep dis

in the 5-C

that neur

s of the 5

has effects

mmer et a

et al., 2006

ute sleep d

tive task b

pter 3, 4 an

ws for clos

elective att

gest that a

oural contr

nd Dinges

(Harrison

al., 1992)

p deprivat

task (5-C

respond t

ood reward

to detect

s sustaine

ddition, be

onses) are

inhibitory c

or perseve

ehavioural

visual stimu

elective att

uous perfo

ari et al., 2

sturbance,

CSRTT tra

robiologica

5-CSRTT,

on the und

al., 1992; H

6). Therefo

deprivation

y using th

nd 5) but b

se observa

tention, su

attentional

rol process

, 2005), s

and Horne

without a

tion has d

SRTT) wa

to a light s

d. In this ta

the stimu

ed and s

ecause res

e counted a

control and

erative resp

control. A

ulus can be

tention as

ormance te

2008). In h

which ma

anslational

al mechan

by use of

derlying

Harrison

ore, the

affects

e same

by using

ation of

ustained

deficits

ses that

such as

e, 1999)

affecting

different

as used.

stimulus

ask, the

lus and

elective

sponses

as error

d allows

ponding

Also, the

e varied

well as

est and

humans,

kes the

to the

isms of

f lesion

studies

task (R

previou

perform

impairm

prolong

W

depriva

study a

by redu

loss pe

to ens

assess

proced

of the

sleep t

extent

keep t

depriva

study m

were a

Stress-

for, by

simulta

2004; G

to dete

attentio

s and phar

Robbins, 20

us articles

mance (Go

ment on d

ged parado

While the

ation affec

aimed to s

ucing the p

er se. Ther

ure that t

sment. Mor

ure. Studie

stress sys

times signi

of HPA ax

the anima

ation proce

measured

affected by

-confoundi

y radiote

aneously a

Greene et

ermine in a

onal proces

rmacologic

002; Dalle

have inv

odoi et a

different at

oxical slee

study of C

cts the 5-C

how the e

possibility t

refore, a 1

the stress

reover, the

es in our la

stems whe

ificantly (C

xis and ad

ls awake

edure, po

locomotor

y acute sl

ng effects

elemetry u

and continu

al., 2007;

a non-conf

sses in the

cal agents

y et al., 20

estigated

al., 2005;

ttentional

p deprivati

Cordova an

CSRTT pe

effect of ac

that stress

.5-h recov

systems

e present s

ab showed

en animals

Chapter 3

drenalin ac

(Dobrako

lysomnogr

r activity an

leep depri

of the sam

using a

uously the

Tang et al

founded wa

e 5-CSRTT

that influe

004; Dalley

the effects

Cordova

parameter

ion.

nd co-work

rformance

cute sleep

systems a

very period

were bac

study used

d that this

s were ha

and 4). Ha

ctivation ca

vova et a

raphic par

nd body te

ivation and

mpling pro

small im

e paramete

., 2007). U

ay how ac

T.

Sleep dep

ence one

y et al., 20

s of sleep

et al., 2

rs after ac

kers alread

(Cordova

deprivatio

are activate

d after slee

ck to contr

d a gentle

method ind

abituated b

abituation

aused by t

al., 1993).

rameters w

emperature

d subsequ

ocedure we

mplantable

ers in freel

Using these

cute sleep

privation a

or more p

008; Bari e

p disturban

2006). Bot

cute sleep

dy showed

a et al., 20

n in a non

ed by othe

ep depriva

rol levels

e handling

duced only

but noneth

to handlin

the gentle

To contr

were mea

e levels to

uent 5-CS

ere reduce

transmitt

ly-moving

e methods

deprivatio

and the 5-

parameters

et al., 2008

nce on 5-

th studies

p deprivati

d that acut

006), the

n-confound

er factors a

tion was in

before 5-

sleep dep

y a mild ac

heless did

ng will red

handling

rol for the

asured. Als

o show how

RTT asse

ed, and co

ter to m

rats (Leon

, this study

n affects d

CSRTT

121

s of the

8). Two

-CSRTT

s found

on and

te sleep

present

ded way

as sleep

ncluded

-CSRTT

privation

ctivation

reduce

uce the

used to

e sleep

so, this

w these

essment

ontrolled

measure

n et al.,

y aimed

different

Chapte

122

METHO

Anima

At the

Horst,

(see ex

polycar

constan

light/da

animals

Food a

recove

commit

Experi

Animal

trained

animals

respon

duratio

two ex

conditio

protoco

correct

set-ups

animals

into two

day an

circadia

sleep-d

Statistic

er 6

ODS

ls and hou

beginning

The Nethe

xperimenta

rbonate ca

nt tempera

ark regime

s were han

access was

ry of surge

ttee approv

mental de

s were fir

after a r

s survived

se accura

n of 0.5 s

xperimenta

ons (n=10)

ol that will

t response

s were use

s could be

o groups,

nd 24-h re

an time po

deprived an

cal analys

using

g of the e

erlands), w

al design s

ages conta

ature (21 ±

e using a 3

ndled daily

s restricted

ery, rats ha

ved all exp

esign

rst trained

recovery p

surgery a

acy, ≥45 c

. Twenty-o

al groups:

). The othe

l not be fu

es and om

ed in para

e tested in

using a ba

ecovery o

oints. These

nd assesse

is showed

experiment

weighing 38

section be

ining bedd

± 1°C), con

30-min dim

y for weighi

d to approx

ad full acc

perimental

in the 5-

period unt

and fulfilled

correct res

one rats w

6-h slee

er 11 anim

urther des

missions w

allel to redu

n the 5-CS

alanced de

n different

e two grou

ed after ea

d no signifi

t 62 adult

85 g on av

elow). The

ding and ca

trolled hum

m/rise per

ing purpos

ximately 15

ess to food

protocols.

-CSRTT, t

til reaching

d the crite

sponses a

were pseud

p deprivat

mals were u

scribed he

ere match

uce variab

SRTT simu

esign, that

t days in

ups were d

ach other in

cant effec

male Spr

verage, we

animals w

age enrichm

midity (50 ±

iod with lig

ses and wa

5 g of labo

d prior to r

then receiv

g a stable

eria of stab

and ≤ 20%

do random

tion (n=11

used to val

re. The av

hed betwee

bility amon

ultaneously

t had their

the same

ivided into

n the 5-CS

t of testing

rague-Daw

ere trained

were indiv

ment. The

± 10%) and

ghts on a

ater was pr

ratory chow

re-training.

ved surge

e performa

ble perform

% omission

ly assigne

1) or non

lidate a sle

verage res

en groups

ng animals

y, the anim

baseline d

e week bu

two subgr

SRTT with a

g day, time

wley rats (

d in the 5

vidually ho

room was

d a fixed 1

t 06.00 a.

rovided ad

w per day.

. The local

ery, and w

ance. In t

mance with

ns on a s

d to the fo

-deprived

eep fragme

sponse ac

s. Eight 5-

s. Because

mals were

day, exper

ut at com

roups, whic

a delay of

e or 45-mi

(Harlan,

CSRTT

used in

s kept at

2 : 12 h

m. The

libitum.

. During

l ethical

were re-

total 32

h ≥50%

stimulus

ollowing

control

entation

ccuracy,

-CSRTT

e only 8

divided

rimental

parable

ch were

45 min.

n delay

on all m

baselin

decrea

perseve

resulted

control

phase,

On the

circadia

30 min

at light

followe

left und

Followi

which

recove

electro

5-choic

Appara

Trainin

30.5 cm

in soun

2.5 cm

grid flo

of eac

dispens

purified

tray. A

All hole

front) to

measurem

ne compare

sed comm

erative re

d in a dist

condition

i.e. the re

e baseline

an time po

baseline t

ts-on or 45

ed by a 1.5

disturbed

ng the 5-C

rats were

ry of sleep

myographi

ce serial r

atus

g and test

m x 24.1 c

nd-isolated

x 2.2 cm)

or. A light

ch hole. T

ser. Highly

d diet, Bio

yellow ho

es includin

o detect no

ments. The

ed to their

menced a

sponses.

ribution of

ns. All exp

sting phas

day, the

oints as for

telemetric

5 min afte

5-h post-d

in their ho

CSRTT, rat

re-tested

p deprivatio

ic (EMG) w

reaction ti

ting for the

cm x 29.2 c

d and venti

were loca

stimulus (

The oppos

y palatable

-Serv, Fre

ouse light (

ng the foo

ose pokes

refore the

r 5-CSRTT

and compl

These rat

f n=10 for

perimental

se and pote

animals w

r the exper

measurem

er lights-on

eprivation

ome cages

ts were left

in the 5-C

on period,

were contin

me task

e 5-CSRTT

cm (Med A

lated enclo

ated on the

(LED, 6.4 m

site wall c

e food pel

enchtown,

(LED, 28 V

d tray wer

and food

data of a

T performa

leted trials

ts were e

6-h sleep

procedur

entially dis

were asses

rimental da

ments, follo

n or non-d

recovery

s, followed

t undisturb

CSRTT. Du

locomotor

nuously reg

T were co

Associates

osures. Fiv

e curved re

mm diame

contained

lets (Dustl

USA) wer

V, 100 mA

re equippe

collection.

Sleep dep

all groups w

ance during

s and tw

excluded f

deprivatio

res were

sturbing sti

ssed in th

ay. The ex

owed by 6-

deprived c

phase dur

d by 30-m

bed during

uring the

r activity, b

gistered.

nducted in

s Inc, Geor

ve evenly

ear wall of

eter, 28 V)

a food tr

less precis

re automat

) was pos

ed with inf

. The appa

privation a

was taken

g training d

wo rats sh

from all a

n and n=8

performed

muli were

e 5-CSRT

xperimenta

-h sleep de

ontrol con

ring which

in testing

a 24-h rec

experimen

body tempe

n operant b

rgia, USA)

spaced ap

the chamb

was posit

ray, conne

sion pellet

tically deliv

itioned abo

frared bea

aratus was

and the 5-

n together.

days, one

howed ex

nalyses a

8 for non-d

during th

carefully a

TT at com

al day start

eprivation

nditions. Th

all anima

in the 5-C

covery peri

ntal day an

erature, E

boxes, me

that were

pertures (2

ber, 2 cm f

tioned at th

ected to a

ts, 45 mg

vered in th

ove the fo

ams (1.0 c

s controlled

CSRTT

123

During

rat had

xcessive

and this

deprived

he light

avoided.

parable

ted with

starting

his was

als were

CSRTT.

od after

nd 24-h

EG and

easuring

e placed

2.5 cm x

from the

he back

a pellet

Rodent

he food

od tray.

cm from

d by the

Chapte

124

comput

above

observa

Protoco

The pro

and co

done o

15 pre

reinforc

boxes w

to habi

training

switche

pellet. A

tray to

correct

respon

initiated

into the

poke in

was pr

limited

failures

(prema

without

on and

respon

perseve

100 tria

in the s

was ini

er 6

ter progra

the 5-CS

ational ana

ol

otocol for

-workers (

n weekday

ecision pel

cer. During

with 15 pre

tuate them

g phase co

ed on. Any

After a no

start a ne

t nose pok

d to a sing

d by a nos

e food tray

nto the foo

resented in

hold (LH)

s to respon

ature respo

t delivery o

d the rat sh

ses in the

erative res

als had be

same box

tially set a

am MED-P

SRTT box

alysis. For

5-CSRTT

Bari et al.,

ys. At the f

lets in the

g the follow

ecision pel

m to the bo

onsisted of

y nose po

ose poke, a

ew trial. Aft

kes within

gle visual s

se poke in

y at the be

d tray initia

n one of t

period wa

nd (omissio

onses) wer

of a precisi

hould poke

five holes

sponse, bu

en comple

throughou

at 30 s, wit

PC IV (Me

x to mak

this study,

training w

, 2008). Tr

first day of

eir home

wing two da

llets in the

oxes and th

f four days

ke in an a

all lights w

ter four tra

the 30-m

stimulus pr

nto the foo

eginning o

ated an int

the five ho

as rewarde

ons) and re

re punishe

ion pellet.

e in the foo

s after the

ut were no

eted, which

ut the train

th an ITI o

ed Associa

ke record

, the record

as adapte

raining and

f food restr

cages to

ays, rats w

food tray

he place w

s of 30-mi

arbitrary ho

were switch

aining days

in session

resented in

od tray. An

of each se

ter-trial inte

oles. A co

ed with a

esponses

ed with a 5

After a TO

od tray to

presentat

t punished

hever occu

ning and t

f 10 s, a L

ates Inc.).

ings durin

dings were

d from the

d testing in

riction, rats

familiarize

were placed

and the ho

where the r

n sessions

ole was re

hed off unt

s the rats

n. Subsequ

n one of th

n initial pre

ession to in

erval (ITI),

rrect nose

precision

before pre

5 s period

O period, th

start a new

tion of a st

d. Each se

urred first.

esting pha

LH period o

A camera

ng a ses

e not analy

e protocol d

n the 5-CS

s were give

e them to

d for 20 mi

ouse light

reinforcer i

s with all l

ewarded w

til the rat p

reached a

uently, rats

e five hole

ecision pel

nitiate the

after whic

e poke in t

pellet. Inc

esentation

of darkne

he house-l

w trial (Fig

timulus we

ession laste

Each rat w

ases. The

of 10 s. Af

a was pos

ssion for

ysed.

described

RTT were

en addition

the taste

n in the 5-

were switc

is given. T

ights in th

with one p

poked in t

an average

s were tra

es. Every t

llet was de

first trial.

ch a light s

this hole w

orrect resp

of a light s

ess (time-o

ight was sw

gure 1). Re

ere recorde

ed 30 min

was always

stimulus d

fter five da

sitioned

further

by Bari

always

nally 10-

e of the

-CSRTT

ched on

The next

e holes

recision

he food

e of 200

ained to

rial was

elivered

A nose

stimulus

within a

ponses,

stimulus

out, TO)

witched

epeated

ed as a

or until

s tested

duration

ays, rats

Figin tin orewreswitpeRea p

reache

respon

and les

1 s. A

rats ha

rats we

decrea

≥50% r

and tes

Analysi

To asse

• C

• C

•

gure 1. Schethe food trayone of the fivwarded with sponses befoth a period oriod, the ho

epeated respperseverative

d an a

ses/(#corr

ss than 1%

After 7-9 da

ad 7-11 da

ere re-trai

sing to 0.2

response a

sting was d

is

ess 5-CSR

Commenc

Completed

Response

ematic overvy, initiating anve holes. A ca precision pore presenta

of darkness (ouse-light waponses in thee response, b

average

ect respon

% omission

ays on 1 s

ys to reco

ined, start

25 s (Table

accuracy, ≥

done on 0.5

RTT perfor

ced trials: n

d trials: num

accuracy:

view of a trialn inter-trial incorrect nose pellet. Incorration of a st(time-out) wias switchede five holes abut are not p

response

nses + #in

ns. Then th

s stimulus d

ver with fu

ting one d

e 1). Since

≥45 correc

5-s stimulu

mance the

number of c

mber of co

number o

l in the 5-CSnterval (ITI), apoke in this

rect responsetimulus lightthout deliver on and theafter the prespunished.

e accura

ncorrect re

he stimulus

duration, r

ull access

day on 1

rats show

ct response

us duration

e following

correct + in

orrect + inc

of correct re

Sleep dep

SRTT. A trial after which ahole within aes, failures tt (prematurery of a precise rat is allosentation of

cy (as

esponses))

s duration

rats underw

to food. A

0-s stimul

wed a stable

es and ≤ 2

n, 5-s ITI, 5

variables w

ncorrect +

correct resp

esponses/(

privation a

starts when a stimulus liga limited holdto respond (oe responses)sion pellet. Aowed to staa stimulus a

indicated

)*100%) of

was gradu

went surge

After recov

lus duratio

e performa

20% omiss

5-s LH and

were analy

premature

ponses

(completed

and the 5-

the rats pokht is present

d (LH) periodomissions) a) are punishAfter a time-ort a new tr

are recorded

d by (#

f more tha

ually decre

ery. After s

very from s

on and gr

ance on 0.

ions, final

d 5-s TO pr

ysed:

e + omissio

d trials)*10

CSRTT

125

kes ted d is and hed out ial. as

#correct

an 80%

eased to

surgery,

surgery,

radually

5 s with

training

rotocol.

ons

00%

Chapte

126

• t

• uo

•

• st

• Cc

These

1.5 h a

of slee

baselin

the gro

T

er 6

Percentagtrials)*100

Errors of ounit (=stomissions/

PrematureITI: numbe

Perseverastimulus htrials)*100

Correct recorrect nos

measures

after the ter

ep depriva

ne was als

oup mean.

Table 1. 5-CS

Stimulus

Duration (s

30

10

2

1

1.5

1.2

1

10

2

1.5

1.2

1

0.5

0.25

0.5

e correct %

omission, ftimulus /(commenc

e responseer of prema

tive respohas occur%

esponse lase poke.

were ass

rmination o

ation. For

o calculate

SRTT trainin

s)

Inter-t

interva

10

5

5

5

5

5

5

5

5

5

5

5

5

5

5

response

failing to reduration

ced trials)*

es, responsature respo

onses, reprred: num

atency: the

essed for

of the slee

persevera

ed for eac

g schedule b

rial

al (s)

Lim

hold

10

5

5

5

5

5

5

5

5

5

5

5

5

5

5

es: numbe

espond to + limit

*100%

se prior to onses/(com

peated rember of p

e time bet

the baseli

p deprivat

ative respo

ch individua

before and af

ited

d (s)

Time

(s)

5

5

5

5

5

5

5

5

5

5

5

5

5

5

5

r of corre

a stimulusted hold

the onset mmenced t

esponses erseverativ

tween ons

ne day, th

ion proced

onses, the

al and an

fter surgery,

e-out Days

(nr)

5

1

5

7-9

1

1

7-9

1

1

2

1

9

6

6

5-8

ect respon

s within thd period

of the targtrials)*100%

at the hove respon

set of ligh

e experim

dure and af

e change

average w

in chronolog

s Comm

After

nses/(comm

e prescrib): numb

get stimulu%

oles afternses/(comm

ht stimulus

ental day

fter 24 h re

as compa

was calcula

gical order

ments

surgery

menced

ed time ber of

s in the

r visual menced

s and a

starting

ecovery

ared to

ated for

Sleep d

Sleep d

period

analyse

deprive

signs o

moved

cage fo

animals

the exp

home c

Surger

After s

with ele

O2-N2O

0.1 ml/

transm

implant

to be

abdom

muscle

cortical

contact

to breg

2007).

deprivatio

deprivation

for one su

es showed

ed by the g

of sleep, th

. When thi

or a few

s to handli

perimental

cages in th

ry

successfull

ectrodes to

O-isoflurane

/100 g bod

itter (TL11

ted which

measured

inal cavity

es (cervical

l EEG me

t with the d

gma and a

After surge

on

n was indu

ubgroup an

d no effec

gentle han

e lid of the

s did not r

seconds (

ng, they w

day. Con

he same ro

y finishing

o allow for

e anaesth

dy weight)

M2-F20-E

allowed bo

. The bod

. Two biop

l trapezius

easuremen

dura at 3 m

anchored t

ery, the an

uced for 6

nd starting

ct of the 4

ndling meth

e cages wa

result in vis

(Grassi-Zu

were handle

ntrol rats w

oom.

g 5-CSRTT

r EEG and

hesia. The

was adm

EET, DataS

ody tempe

dy of the

potential lea

) for EMG

nts were le

mm on eith

to the sku

nimals were

6 h starting

g 45 min la

45-min del

hod. When

as lifted or

sual activa

ucconi et a

ed for at le

were left u

T training,

EMG reco

analgesic

ministered s

Sciences I

erature, gro

transmitter

ads were b

registratio

ed subcut

er side late

ll with scre

e allowed t

Sleep dep

g at the be

ater for the

ay on all

never the

the anima

tion of the

al., 2006).

east 10 min

undisturbed

animals

ording. Su

c Piritramid

subcutane

nternationa

oss locomo

r was plac

bilaterally a

on. The oth

taneously

eral to the

ews and d

to recover

privation a

eginning o

e other sub

measurem

animal sho

al was stro

animal, it

. In order

n on the tw

d and non

were chro

urgery was

de (dipido

ously at s

al, St. Pau

otor activit

ced intrap

attached to

her two bio

to the sku

midline an

dental cem

for 7-11 d

and the 5-

of the 30-m

bgroup. St

ments. Sle

owed beha

ked on its

was lifted

to habitu

wo days pre

n-deprived

onically im

s performed

lor, 0.025

tart of sur

ul, MN, US

y, EEG an

peritoneally

o the deep

potential le

ull and pla

nd 6 mm p

ment (Tang

ays.

CSRTT

127

min rise

tatistical

ep was

avioural

back or

from its

ate the

eceding

in their

mplanted

d under

mg/kg,

rgery. A

SA) was

nd EMG

y in the

per neck

eads for

aced in

posterior

g et al.,

Chapte

128

Biotele

Gross

telemet

depend

obtaine

Becaus

animal

were re

upright

using D

sample

and loc

depriva

sleep d

calcula

EMG a

analyse

Flaga,

Interna

concur

betwee

presen

range

Movem

a domi

lack of

irregula

muscle

signals

distribu

wakefu

calcula

depriva

er 6

emetric da

locomoto

trically me

dent frequ

ed by coun

se the tra

were hard

eceived by

position a

Dataquest

ed in 10-s e

comotor a

ation, for t

deprivation

ated for the

and EEG

es were d

Reykjavi

ational). Th

rent EEG

en states. N

ce of high

(0.5-4 Hz

ment (REM

nance of t

f muscle t

ar low-amp

e tone and

s, the vigi

ution of co

ulness, NR

ated for th

ation with

ata acquis

or activity

easured. T

ency mod

nting the n

nsmitter w

dly detecte

y an anten

at one side

Labpro sof

epochs an

ctivity data

he 6-h sle

n period a

e same ani

recordings

done by v

ik, Icelan

he vigilanc

power spe

Non-Rapid

h amplitude

) and low

) sleep wa

theta activi

one with o

plitude, fas

d frequent

lance data

ontrol n=4

REM and R

he 15 mi

subsequen

sition and

, body t

he transm

dulated sig

number of

was implan

ed by the

nna board

e of the 5-C

ftware. Bod

nd average

a were ca

eep depriva

nd during

imals as th

s were sa

visual scor

nd) and

ce states

ectrum for

d Eye Mov

e EEG wa

w muscle t

as characte

ity (4.5-8 H

occasiona

st EEG wit

body mov

a of some

and sleep

REM sleep

n precedi

nt 1.5 h re

analysis

emperatur

itter emitte

gnals. For

f changes

nted in th

receiver, b

placed u

CSRTT bo

dy tempera

ed and stor

lculated fo

ation perio

the first 2

hose for wh

ampled at

ring using

NeuroSco

were det

r each epo

vement (NR

aves and p

tone and

erized by h

Hz) with re

l twitches.

th a lack o

vements. D

e rats cou

p deprivatio

p was calc

ng sleep

ecovery of

re, cortica

ed body te

r gross loc

in signal

e abdome

but horizo

nderneath

ox and wer

ature and

red into 5-

or the 15-m

od with su

20 min of

hich 5-CSR

a rate o

Somnolog

ore Vers

termined o

och was u

REM) slee

predomina

lack of bo

highly regu

educed low

Wakefuln

of visible th

Due to art

uld not be

on n=8. Th

culated in

deprivatio

f sleep de

al EEG a

emperature

comotor a

strength o

en, vertica

ntal chang

the home

re process

locomotor

min bins. B

min period

bsequent

the 5-CSR

RTT result

f 250 Hz.

gica Versi

sion 2.0.0

off-line in

sed to aid

p was sco

ant EEG p

ody move

ular low am

wer frequen

ness was

heta domin

efacts in t

e analyse

he amount

15-min blo

on and fo

privation.

and EMG

e, EMG an

activity, da

of the tran

l changes

ges were.

e cage an

ed by a co

activity da

Body temp

d precedin

1.5-h reco

RTT. Thes

ts are show

. EEG an

on 3.2 (M

0 (DataS

10-s epo

d in discrim

ored based

power in th

ment. Rap

mplitude EE

ncies and

scored ba

nance, and

the EEG o

ed, resultin

t of time s

ocks. Thes

or the 6-h

Due to too

G were

nd EEG

ata was

nsmitter.

s of the

Signals

d in an

omputer

ata were

perature

g sleep

overy of

se were

wn. The

d EMG

Medcare

ciences

ochs. A

minating

d on the

he delta

pid Eye

EG with

general

ased on

d higher

or EMG

ng in a

spent in

se were

h sleep

o many

artefac

signals

starting

deficit w

Hz wa

Transfo

Statist

All data

Geisse

assump

sleep d

signific

points

distribu

analysi

post-de

phase,

sleep

analyse

done fo

check f

results

depriva

The 5-

day, 24

the ba

analyse

Differen

SEM.

cts in the

s could not

g 30 min a

was (still)

as analyse

ormation (F

ics

a were sta

er correcti

ption. Trea

deprivation

ant differe

at which

ution, NRE

s was per

eprivation

in order to

deprivation

es did not

or the sle

for an effec

are only s

ation with p

-CSRTT pe

4 h recove

aseline, ex

es were pe

nces were

EEG and

be analys

after termi

present. T

ed using

FFT) at a r

tistically an

on epsilo

atment was

n) and the

ence, post

sleep-dep

EM delta, b

rformed se

phase and

o study the

n on the

show a si

ep depriva

ct in recov

shown and

post-depriv

erformance

ery). Paired

xperimenta

erformed u

e considere

d EMG re

sed and we

nation of

The delta p

Somnolog

resolution o

nalysed by

on (ε) for

s used as

different ti

hoc t-tests

prived and

body temp

eparately f

d for the 5

e effect of

5-CSRTT

ignificant s

ation and

ery. Since

d discusse

vation reco

e was als

d t-tests w

al day an

using SPSS

ed signific

ecordings d

ere conseq

the 5-CSR

power duri

gica Versio

of 0.25 Hz

y repeated

r violation

between-s

ime points

s were per

control a

perature a

for the slee

5-CSRTT

sleep depr

T assessm

sleep depr

post-depri

this did no

ed for the a

overy.

so analyse

were used t

nd 24-h re

S 15.0 sof

cant at p<0

Sleep dep

during 5-C

quently onl

RTT in ord

ng NREM

on 3.2 (M

for 10-s N

measures

n of the

subjects fa

s as within-

rformed to

animals dif

nd locomo

ep depriva

assessme

rivation itse

ment or r

rivation effe

ivation pha

ot give a d

analyses d

ed per per

to determi

ecovery fr

ftware (SP

0.05. Data

privation a

CSRTT as

ly analysed

der to see

sleep in t

Medcare)

NREM slee

s ANOVA w

homogen

ctor (two le

-subject fa

determine

ffered. Fo

otor activit

ation with

ent or sub

elf and the

ecovery.

ect, the an

ase separ

ifference in

done for th

iod (basel

ne the diff

rom sleep

PSS inc., C

a are prese

and the 5-

ssessment

d for 1-h d

whether

he range o

by Fast F

p epochs.

with Green

neity in v

evels; con

actor. In ca

e the speci

r the slee

y respons

subsequen

sequent re

en for the e

If these A

nalyses we

rately, in o

n significan

he period o

ine, exper

ferences b

p deprivat

Chicago, IL

ented as m

CSRTT

129

t, these

uration,

a sleep

of 0.5-4

Fourrier

nhouse-

variance

trol and

ase of a

ific time

ep-wake

es, this

nt 1.5-h

ecovery

effect of

ANOVA

ere also

order to

nce, the

of sleep

rimental

between

ion. All

L, USA).

mean +

Chapte

130

RESUL

Chang

sleep d

Sleep d

Data o

power

h post

respect

differen

non-de

sleep s

During

with a

non-de

time*tre

(F1,10=2

whole

interact

presen

decrea

depriva

was co

from s

increas

(F2,230=

Wakefu

the non

Upon t

control

sleep-d

min up

er 6

LTS

es in slee

deprivatio

deprivation

on time sp

during 6-h

t-deprivatio

tively). Du

nces in tim

eprived con

stayed fairly

sleep dep

concomita

eprived co

eatment in

242.6 p<0.

sleep de

tion was f

t. Post-ho

sed during

ation, NRE

ompletely a

leep. The

ses in tim

=2.6, ε=0.2

ulness dura

n-deprived

termination

levels imm

deprived co

on termina

ep-wake d

on with su

n and cons

pent in wa

sleep dep

on recove

uring the

e spent in

ntrol cond

y stable an

privation a

ant increas

ontrol grou

nteraction

.001). NRE

privation

found but

oc analysi

g most tim

EM sleep re

abolished i

se reduct

me spent

2, p=0.049)

ation was

control co

n of the sl

mediately.

ondition as

ation of the

distributio

bsequent

secutive rec

kefulness,

privation or

ery phase

15 min

wakefulne

itions, the

nd animals

a significan

se in time

up. For N

(F23,230=3

EM sleep

period. Fo

a significa

s showed

e points o

emained b

indicating t

ions in N

awake,

) and a sig

increased

ondition thr

eep depriv

NREM sle

s compare

e sleep de

n and NR

5-CSRTT

covery

NREM a

r the non-d

e are illu

preceding

ess, NREM

time spe

s were asle

nt reductio

spent awa

NREM sle

3.2, ε=0.2

duration w

or REM s

ant treatm

d that RE

f the sleep

below 2 mi

that the ra

REM and

with a s

gnificant tre

for the sle

roughout th

vation proc

eep duratio

ed to the co

eprivation p

REM delta

assessme

nd REM s

deprived co

ustrated in

g sleep

M and REM

ent in wak

eep most o

n in NREM

ake was in

eep, ANO

, p=0.023

was signific

sleep, no

ment effect

EM sleep

p deprivatio

in per 15-m

ats were al

REM sle

significant

eatment ef

eep-deprive

he sleep de

cedure, R

on was sig

ontrol cond

procedure,

power in

ent

sleep and

ontrol cond

n Figure

deprivation

M sleep we

efulness,

of the time.

M and RE

nduced as

OVA show

3) and a

cantly decr

significan

t (F1,10=64

duration

on period.

min interva

lmost cont

eep were

time*treat

ffect (F1,10=

ed conditio

eprivation

EM sleep

gnificantly

dition for 3

with a sig

response

the NREM

dition and t

2 (panel

n, no sig

ere present

NREM an

EM sleep d

compared

wed a sig

treatment

reased du

nt time*tre

.3, p<0.00

was sign

During 6

al and REM

tinuously d

concomita

tment inte

=245.1, p<

on as comp

period.

duration r

increased

30 min sta

gnificant tre

e to 6 h

M delta

the 1.5-

s A-D,

gnificant

t. Under

nd REM

duration

d to the

gnificant

t effect

ring the

eatment

01) was

ificantly

h sleep

M sleep

deprived

ant with

eraction

<0.001).

pared to

reached

for the

rting 15

eatment

effect (

still affe

treatme

duratio

first 15

The de

control

depriva

and als

5-CSR

In orde

CSRTT

and NR

5-CSRT

and the

During

wakefu

wakefu

with re

only a

levels d

duratio

be sign

recove

During

treatme

Post-ho

delta p

the 5-C

(F1,10=13.6

ected upo

ent effect

n was sign

min of the

elta power

condition

ation did no

so not durin

TT consec

er to see w

T, when ra

REM delta

TT. This is

e NREM de

this 1-h

ulness du

ulness, AN

duced wa

significan

during mos

n also sho

nificantly i

ry period.

the hour

ent effect w

oc analysis

ower for th

CSRTT.

6, p=0.004)

n terminat

(F1,10=15.0

nificantly d

e post-depr

r during N

s through

ot affect N

ng the 1.5-

cutive reco

whether a

ats were re

power we

s illustrated

elta power

period, th

ration wit

OVA show

kefulness

nt treatmen

st of the 1

owed a sig

ncreased

starting 3

was found

s showed

he sleep-de

) but no in

tion of the

0, p=0.003

ecreased

rivation rec

NREM sle

out the ex

NREM delta

-h post-dep

very

sleep defi

eturned to

re analyse

d for the tim

r in Figure 2

he sleep-d

th increas

wed only a

duration d

nt effect w

-h recover

nificant tre

(p<0.01) f

30 min af

(F1,10=5.0

only a tre

eprived an

nteraction e

e sleep de

3). Post-ho

by sleep d

covery peri

ep remain

xperimenta

a power d

privation re

icit was st

o their hom

ed for 1-h s

me spent in

2 (panels A

eprived a

sed NREM

significant

during mos

was found

ry of 5-CS

eatment eff

for the las

fter termin

, p=0.049)

end to sign

nimals for 1

Sleep dep

effect. Also

privation p

oc analysis

deprivation

iod.

ned fairly

al period

uring the 6

ecovery pe

till present

me cages,

starting 30

n wakefuln

A-D, respe

nimals sh

M and R

t treatmen

st of this h

(F1,9=10.0

RTT perio

fect (F1,9=8

st 45 min

nation of t

) for the NR

nificance (p

15 min sta

privation a

o wakefuln

procedure

s showed

for 45 min

stable un

(Figure 2

6-h sleep d

eriod.

upon term

the sleep-

min after

ness, NREM

ectively).

owed sign

REM slee

t effect (F1

hour. For N

0, p=0.012

od. Further

8.6, p=0.01

of this 1

the 5-CSR

REM delta

p=0.059) w

rting 1 h a

and the 5-

ness durati

with a sig

that wake

n starting f

der non-d

panel D)

deprivation

mination of

-wake dist

terminatio

M and REM

nificantly r

ep duratio

1,9=12.7, p

NREM sle

2) with inc

more, REM

17) and te

-h post-5-

RTT, a sig

a power res

with lower

fter termin

CSRTT

131

ion was

gnificant

efulness

rom the

deprived

. Sleep

n period

f the 5-

tribution

n of the

M sleep

reduced

on. For

=0.006)

ep also

creased

M sleep

nded to

-CSRTT

gnificant

sponse.

r NREM

nation of

Chapte

132

NR

EM

del

ta p

ower

(V

2)

0,00

0,05

0,10

0,15

0,20

RE

M s

leep

(m

in)

0

5

10

15

NR

EM

sle

ep

(min

)

0

5

10

15

Wa

kefu

lne

ss (

min

)

0

5

10

15

FigureREM ssleep and tharea bupon tas 15-condit

er 6

-40 0

-40 0

-40 0

A

B

C

D

e 2. Time cosleep (panel deprivation

he 1.5-h recobetween the termination o-min averageion (n=8). Si

40 80

40 80

*

40 80

* *

urse of chan C) and NREor non-depriovery perioddashed lines

of the 5-CSRes + SEM angnificance: s

120 160

120 160

*

120 160

*

*

nges in the aEM delta powived control . Subsequens) of which p

RTT, the parand are shownsleep depriva

Time (m

200 240 2

200 240 2

200 240 2

*

amount of wawer (panel Dperiod (indic

nt is the 30-mpolysomnogrameters are n for the contation versus

min)

280 320 3

280 320 3

*

280 320 3

akefulness (pD) during thecated by themin 5-CSRTraphic recordshown for antrol conditioncontrol *p<0

60 400 44

360 400 44

360 400 44

*

*

*

**

CoSle

panel A), NR 15-min bas

e area betweTT assessmedings were nnother hour. n (n=4) and t.05.

40 480 520

40 480 520

40 480 520

*

*

ntrol (n=4)eep deprivatio

REM sleep (peline period,

een the dotteent (indicatednot analysed

Data are exthe sleep dep

0 560

0 560

0 560

* *

* *

on (n=8)

panel B), , the 6-h ed lines) d by the . 30 min

xpressed privation

Dynam

sleep d

Sleep d

Data o

depriva

recove

Under

beginn

depriva

increas

signific

p<0.00

sleep

signific

(F1,16=1

only sig

to the c

Under

during

sleep d

h sleep

ε=0.1,

temper

increas

sleep d

temper

p<0.00

termina

reachin

depriva

mics of th

deprivatio

deprivation

on locomo

ation or th

ry phase a

non-depriv

ing of the

ation, indic

se in loco

ant time*tr

1). Activity

deprivation

ant time*t

10.6, p=0.0

gnificantly

control gro

non-depriv

the sleep

deprivation

p deprivati

p=0.005),

rature incr

sed within

deprivation

rature sho

1), with n

ation and

ng levels s

ation recov

he locomo

on with su

n and cons

otor activit

he non-de

are illustrat

ved contro

sleep dep

ating overa

omotor act

reatment i

y levels w

n period.

reatment

005) was p

decreased

up.

ved control

deprivatio

n period (p

on, a sign

, with a

reased gr

25 min an

n period. U

owed a s

no treatm

took 20 m

significantly

very period

otor activ

bsequent

secutive rec

ty and bo

eprived co

ed in Figur

ol condition

privation pe

all inactivit

tivity levels

nteraction

were increa

During th

interaction

present. Po

d for 5 min

l conditions

on period

=0.003). S

nificant tim

significant

radually u

d continue

Upon termin

ignificant

ment effect

min to reac

y below co

ity and b

5-CSRTT

covery

ody tempe

ntrol cond

re 3 (pane

ns, locomo

eriod and r

ty of these

s above c

and a sig

ased almos

he 1.5-h p

n was foun

ost-hoc an

n at the end

s, body tem

as compa

Stable valu

e*treatmen

t treatmen

pon sleep

ed to be el

nation of t

time*treat

t. Body t

ch control

ontrol leve

Sleep dep

body temp

assessme

erature re

dition and

ls A-B, res

tor activity

remained s

animals. D

control lev

gnificant tre

st at every

post-depriv

nd, but a

alysis show

d of this re

mperature

red to the

es were e

nt interacti

nt effect (

p deprivat

levated du

the sleep d

ment inte

emperatur

levels and

els during

privation a

perature r

ent

sponses d

the 1.5-h

spectively).

y levels we

stable and

During slee

vels was

eatment ef

y time poi

vation rec

significant

wed that a

ecovery pe

was signif

e 30 minut

ventually r

ion was fo

(F1,16=6.6,

tion and

ring most

deprivation

raction (F

re decreas

d then kep

the last 5

and the 5-

response

during 6-h

h post-dep

.

ere low bef

d low durin

ep depriva

induced, w

ffect (F1,16

nt during

overy per

t treatmen

activity leve

eriod as co

ficantly dec

tes preced

reached. D

ound (F71,1

p=0.021)

was sign

time point

n procedur

F17,272=7.3,

sed slowly

pt on decr

5 min of th

CSRTT

133

to 6 h

h sleep

privation

fore the

ng sleep

ation, an

with no

=124.9,

the 6-h

riod, no

nt effect

els were

mpared

creased

ding the

During 6

136=1.8,

). Body

ificantly

s of the

re, body

ε=0.2,

y upon

reasing,

he post-

Chapte

134

Figureresponperiod recovedashedconditiocontrol

5-CSR

Data o

min of

respect

During

termina

differen

Also bo

control

the tas

treatme

p<0.00

presen

Bod

y T

em

pera

ture

(°C

)

36

37

38

39

Act

ivity

(co

unts

/min

)

0

10

20

30

40

er 6

e 3. Time counses during

(indicated bry phase andd lines). Daton (n=8) and *p<0.05.

TT

n the loco

f 5-CSRT

tively).

the first

ation of th

nce was fo

ody tempe

animals h

sk as comp

ent effect (

1) as anal

t before th

-40 0

A

B

urse of chanthe 30-min by the area d the first 20ta are expred the sleep

omotor act

TT assess

20 min

he sleep d

und betwe

erature inc

had a signi

pared to th

(F1,16=5.1,

ysed durin

e animals

*

40 80

*

nges in locombaseline pebetween th

0 min of the 5essed as 5-deprivation

ivity and b

sment are

of the 5-

deprivation

een the sle

reased du

ificantly low

he sleep-d

p=0.038)

ng the first

were expo

*

120 1

*

motor activityriod, the 6-h

he dotted lin5-CSRTT ass-min averagcondition (n

body temp

e also illu

CSRTT a

n, the loco

ep-deprive

ring the fir

wer body t

deprived a

and a sign

20 min of

osed to the

*

Time (m

60 200

*

*** ** *

y (panel A) h sleep dep

nes) with susessment (in

ges + SEM =10). Signifi

perature re

ustrated i

assessmen

omotor ac

ed and con

rst 20 min

temperatu

nimals. AN

nificant tim

f the task.

e 5-CSRTT

min)

240 280

** * *

and body teprivation or nbsequent 1.

ndicated by tand are sh

icance: sleep

esponses d

n Figure

nt starting

ctivity leve

ntrol anima

n of the 5-C

re during t

NOVA sho

e effect (F

This differ

T.

320 360

*** *** *

ContSleep

emperature (non-deprived5-h post-dehe area betw

hown for thep deprivation

during the

3 (panel

1.5 h af

els increas

als.

CSRTT ta

the first 15

owed a sig

F3,48=115.1

ence was

0 400 4

**

rol (n=8)p deprivation

panel B) d control privation

ween the e control n versus

first 20

ls A-B,

fter the

sed. No

sk. The

5 min of

gnificant

, ε=0.7,

already

440 480

*

*

**

*

n (n=10)

5-CSRT

Table 2

on the

sleep d

depriva

respon

time*tre

that the

over th

signific

showed

control

recove

decrea

baselin

animals

compa

differen

When

baselin

presen

analysi

sleep-d

(p=0.01

(p=0.05

TT perform

2 shows th

baseline d

deprivation

ation. For

ses and

eatment in

ese respon

he days fo

ant time*t

d no sign

condition

ry. Paired

se in pers

ne day (p=

s, a trend

red to the

nces were

expressing

ne, as show

t but a sig

s showed

deprived an

19) and a

55).

mance

he 5-CSRT

day, on th

n or non-

the respo

correct

nteractions

nses were

or both gr

reatment i

nificant diff

either on t

d t-tests h

severative

=0.028) as

to a sign

baseline d

present an

g these p

wn in Figu

gnificant tr

a significa

nimals as

close to si

TT perform

e experim

-deprived

onse accur

response

, no time e

not affecte

roups. For

interaction

fference b

the baselin

however s

responses

s is shown

nificant inc

day (p=0.0

nymore.

erseverativ

re 4 panel

reatment e

ant increas

compared

gnificant in

mance of th

ental day

procedure

racy, corre

e latency,

effects and

ed by slee

r persever

(F2,32=4.8

between th

ne day, on

showed fo

s on the e

n in Figure

crease was

094). After

ve respon

B, no sign

effect was

sed chang

to the con

ncrease af

Sleep dep

he control

starting 1.

and afte

ect respon

, ANOVA

d also no t

p deprivati

rative resp

8, ε=0.8, p

he sleep-d

the exper

or the con

experiment

e 4 panel

s found o

24 h recov

nses as th

nificant tim

found (F1

ge in perse

ntrol anima

fter 24 h re

privation a

and sleep-

.5 h after t

er 24 h re

nses, omis

A showed

treatment

ion and did

ponses, A

p=0.021). P

deprived a

rimental da

ntrol anim

tal day as

A. For th

n the exp

very of sle

he change

me*treatme

,16=7.1, p=

everative r

als on the

ecovery of

and the 5-

-deprived a

termination

ecovery o

ssions, pre

d no sig

effects, ind

d also not

NOVA sho

Post-hoc a

and non-d

ay or after

mals a sig

compared

he sleep-d

perimental

eep depriva

as comp

nt interact

=0.017). P

responses

experimen

sleep dep

CSRTT

135

animals

n of the

of sleep

emature

gnificant

dicating

change

owed a

analysis

deprived

24 h of

gnificant

d to the

deprived

day as

ation no

ared to

ion was

Post-hoc

for the

ntal day

privation

Chapte

136

Table terminasleep percenthe con

Respo

Correc

Omiss

Prema

Correc

er 6

2. 5-CSRTTation of sleedeprivation.

ntage responntrol (n=8) an

onse accura

ct response

sions (%)

ature respon

ct response

T performancp deprivationThe correc

nses of total nd sleep-dep

acy Co

SD

es Co

SD

Co

SD

nses Co

SD

e Co

SD

ce on the ban or non-dep

ct responsescommenced

prived (n=10)

Ba

ontrol 6

D 6

ontrol 5

D 5

ontrol 2

D 3

ontrol 1

D 1

ontrol 0

D 0

seline day, oprived proces, omissionsd trials, which) animals an

aseline day

65.81±2.59

63.73±2.62

56.13±2.91

54.10±2.87

2.50±0.46

3.10±0.46

2.50±1.43

2.30±1.76

0.76±0.06

0.77±0.04

on the experdures (exp. and prema

h were 100 id are expres

y Experi

da

64.34

67.24

56.25

56.90

3.38±

3.50±

9.38±

12.00

0.78±

0.73±

rimental dayday) and aft

ature responn all cases.

ssed as mea

mental

ay

4±2.51

4±2.75

5±2.74

0±2.66

±0.89

±0.79

±1.28

0±1.45

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24 h recov

CSRTT

137

baseline deprived tal day, control

ange in of sleep e shown : sleep

privation

ep was

w 2 min

e during

privation

dure, a

ction in

T, when

ion with

deprived

awake,

ation of

slightly

very

Chapte

138

increas

were st

a sleep

for mor

are in

deprive

of slee

temper

sleep d

our lab

(Borbe

drive (B

a mar

Neuhau

delta p

measu

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to be

hypothe

1982; B

loss, i.e

short-te

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perform

percen

the 5-C

latencie

motivat

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behavio

were e

in the

er 6

sed their ti

till asleep

p deficit wh

re than 30

accordanc

ed animals

ep depriva

rature may

duration up

b (Chapter

ly, 1998).

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ker for h

us, 1979;

power duri

red during

ermination

decreased

esis that s

Borbely, 1

e. an incre

erm sleep

Despite a

mance of

tage omiss

CSRTT was

es were n

tion for 5

vity of the

ng that the

our upon s

xpressed a

control an

me spent

half the tim

hen asses

min after t

ce with th

s also had

ation and

y also be a

pon 6 h sle

4) and ha

It has bee

d Neuhaus

omeostatic

Franken e

ing NREM

g the 1.5-h

n of the 5-C

d for the

sleep inten

998). Suc

ease in NR

deprivation

significan

the sleep-

sions, num

s not affec

not impaire

-CSRTT p

e animals,

e inhibitory

sleep depr

as change

nimals that

awake as

me. This in

sed in the

termination

e measure

a significa

during 5

a consequ

eep depriv

as also be

en propose

s, 1979). A

c sleep d

et al., 199

M sleep w

h post-depr

CSRTT, the

sleep-dep

sity and sl

ch may im

REM sleep

n of 6 h.

nt sleep d

-deprived

mber of cor

cted. Becau

ed, it can

performanc

as shown

y control w

rivation wa

e to baselin

t decrease

compared

ndicates tha

e 5-CSRTT

n of the 5-C

ed gross

ant lower b

5-CSRTT

ence of th

vation is in

en shown

ed to refle

Also, increa

drive, indic

91; Borbely

was not aff

rivation pe

e delta pow

prived gro

leep durati

mply that a

p duration

deficit, the

rats, as i

rrect respo

use the er

n be conc

ce. Sleep

n by a lack

was not affe

as observe

ne. This e

ed their am

d to before

at the slee

T and that

CSRTT. Th

locomotor

body temp

assessme

he sleep de

n accordan

in previou

ect an elev

ased NREM

cating sle

y, 1998).

fected by

eriod despi

wer during

up. This

ion are se

a quantitati

, is a suff

selective

ndicated b

onses and

rors of om

luded that

deprivatio

k of chang

ected. A s

ed when th

effect was

mount of p

e 5-CSRTT

ep-deprived

this deficit

hese sleep

activity le

perature du

ent. This

epth. The

nce with a

us sleep d

vation in h

M delta po

eep intens

However,

prior slee

ite a NREM

g NREM sle

may be e

parately re

ive compe

icient com

and sust

by the res

correct res

ission and

t there wa

on did als

ge in prem

light increa

he perseve

mainly cau

perseverat

T assessm

d animals s

t was still

p-wake res

evels. The

uring the re

decreased

increased

previous s

eprivation

homeostati

ower is con

sity (Borbe

in our stu

ep depriva

M sleep re

eep even s

explained

egulated (B

ensation fo

mpensation

tained atte

sponse ac

sponse late

d correct re

as no dec

so not aff

mature resp

ase in com

erative res

used by a

ive respon

ment but

still had

present

sponses

e sleep-

ecovery

d body

NREM

study in

studies

c sleep

nsidered

ely and

udy, the

ation as

ebound.

seemed

by the

Borbely,

or sleep

after a

entional

ccuracy,

ency, in

esponse

creased

fect the

ponses,

mpulsive

sponses

change

nses as

compa

increas

compa

rats sh

showed

the no

respon

10 h s

perseve

been a

been in

cortex c

T

show s

2005;

sustain

depriva

2006).

techniq

They s

togethe

There

accoun

studies

D

role. G

h total

for the

The stu

more c

depriva

wherea

(Cordo

red to bas

se the am

red to cont

owed a str

d a small d

on-deprived

ses was a

sleep depr

erative res

attributed t

nitiated. Le

cause an i

The two o

selective an

Cordova

ned attent

ation witho

Godoi and

que thereby

showed im

er with a r

are sever

nt for the d

s.

ifferences

odoi and c

sleep dep

different o

udy of Cor

comparable

ation meth

as our pr

va et al., 2

seline, du

mount of p

trol conditi

rong increa

decrease i

d rats. A

also reporte

ivation; bu

sponses w

o a compu

esions stu

ncrease in

other rat st

nd sustain

et al., 20

ional impa

ut affecting

d co-worke

y inducing

mpaired at

reduced m

al method

different o

in sleep d

co-workers

privation (G

outcomes a

rdova and

e to ours (C

od, but the

ocedure u

2006). Furt

e to unkn

erseveratio

ons. Also,

ase in som

n the amo

lterations

ed in a pre

ut a signifi

was not fo

ulsive inab

udies have

n persevera

tudies com

ed attentio

006). Cor

airments

g motivatio

ers expose

mainly pa

ttentional

motivation a

dological a

outcomes i

eprivation

s used 96 h

Godoi et al

and make

co-workers

Cordova et

eir method

used only

thermore, w

nown reas

on when

analysis o

me rats, wh

ount of per

in inter-in

evious stud

icant overa

und (Cord

bility to dis

e shown th

ative respo

mbining sle

onal deficit

rdova and

in respon

on, impuls

ed rats to 9

aradoxical

performan

and no eff

aspects in

n our stud

procedure

h of REM s

l., 2005). T

it hard to

s used a s

t al., 2006)

d used sen

tactile s

we observ

Sleep dep

on. The s

compared

of individua

hereas othe

severative

ndividual v

dy on 5-CS

all effect o

dova et al.

sengage fr

hat selectiv

onses (Chu

eep depriva

s after slee

co-worke

se to 10

ivity and c

96 h sleep

sleep depr

nce after

fects on im

the use o

dy as com

e and sleep

sleep depr

This essen

further co

sleep depri

). They use

nsory, aud

timulation

ved in prev

privation a

sleep-depr

to baseli

al data of th

ers remain

response

variability

SRTT perfo

of sleep d

, 2006). P

rom respon

ve lesions

udasama e

ation with

ep depriva

ers showe

h gentle

compulsivit

deprivatio

rivation (G

96 h dep

mpulsivity

of the 5-C

mpared to

p deprivatio

rivation wh

ntial differe

mpare tha

ivation me

ed the gen

ditory and

with prev

vious studie

and the 5-

rived rats

ne but did

he sleep-d

ned stable

s as comp

in persev

ormance fo

deprivation

Perseveran

nding once

s in the pr

et al., 2003

the 5-CSR

ation (Godo

ed selectiv

e handling

ty (Cordov

on by the p

odoi et al.

privation o

and comp

CSRTT tha

these two

on duration

hereas we

ence may a

at study wit

thod and d

tle handlin

tactile stim

vious hab

es and als

CSRTT

139

did not

d when

deprived

or even

pared to

verative

ollowing

on the

nce has

e it has

refrontal

3).

RTT did

oi et al.,

ve and

g sleep

a et al.,

platform

, 2005).

of sleep

pulsivity.

at could

o rodent

n play a

used 6-

account

th ours.

duration

ng sleep

mulation

bituation

o in the

Chapte

140

presen

depriva

accumu

by the

Even th

increas

sleep d

2008).

and ex

depriva

h reco

levels

control

confirm

during

(Chapte

this stu

animals

deprive

momen

the sele

found i

state. A

to a dif

maximu

did har

respon

the stu

correct

Godoi

stimulu

howeve

perform

er 6

t study th

ation sessio

ulating slee

sleep dep

hough pub

sed aggres

deprivation

In order t

xercise in

ation was i

very of sl

reached s

levels dur

m that the

this post-

er 3 and 4

udy showe

s still had a

ed rats still

nt the rats

ective and

n the othe

Also, in mo

fference in

um stable

rdly reach a

ses on 0.5

dy of Cord

t response

and co-wo

us duration

er still ab

mance befo

hat some

on (Chapte

ep debt an

privation p

lished stud

ssiveness

n procedur

to eliminat

our expe

ncluded be

leep depri

stable cont

ring the las

physiologi

deprivation

4). The sle

ed that, d

a sleep de

had a slee

were ass

sustained

er rodent st

ost articles

n acquiring

performan

a performa

5-s stimulu

dova and c

s on 0.5-s

orkers a pe

n (Godoi e

bove the

ore they we

rats beca

er 3, 4 and

nd tirednes

procedure

dies do not

have bee

re (Hicks

te possible

eriment, an

efore rats w

vation per

trol levels

st 5 min of

ical and h

n recovery

ep-wake d

despite the

ficit when

ep deficit,

essed in t

d attentiona

tudies are

s, detailed

the task,

nce reache

ance above

us duration

co-workers

s stimulus

erformance

et al., 200

chance le

ere sleep-d

ame agita

d 5). This m

ss, rather t

but future

t mention a

en previou

et al., 197

e confound

n undistur

were asse

riod, body

and body

this recov

hormonal s

y period b

distribution

e 1.5-h re

assessed

but were n

the 5-CSR

al deficits i

the result

training p

difference

ed across d

e 50% res

, even tho

s rats attain

duration (C

e of over

05). The p

evel of 2

deprived.

ated towa

may imply

than a con

e studies a

agitation s

usly reporte

79; Gessa

ding effect

bed recov

ssed in the

y temperat

y temperat

ery period

stress resp

ut that a

data after

ecovery of

in the 5-CS

not in an ag

RTT. This r

n the 5-CS

of some a

rotocols ar

s in cognit

different st

ponse acc

ough the pe

ned 70% re

Cordova e

70% accu

performanc

20% and

rds the e

that agitat

sequence

are needed

pecifically,

ed after te

et al., 19

ts such as

very period

e 5-CSRTT

ture and l

ture even

. Previous

ponses rea

sleep defic

r 6 h of sle

f sleep de

SRTT. The

gitated sta

raises the

SRTT after

animals be

re missing

tive proces

tudies. In o

curacy and

erformance

esponse a

et al., 2006

racy was

ce reached

all anima

end of the

ion is the r

of stress i

d to confir

hyperactiv

ermination

995; Tarta

s stress, a

d following

T. During t

locomotor

decreased

studies in

ach contro

cit is still

eep depriv

eprivation

erefore, the

ate anymor

question w

r sleep dep

eing in an a

, possibly

sses involv

our study, a

over 45%

es were st

accuracy a

6). In the s

reached o

d in our s

als had a

e sleep

result of

induced

rm this.

vity and

n of the

r et al.,

agitation

g sleep

this 1.5-

activity

d below

our lab

ol levels

present

vation in

period,

e sleep-

re at the

whether

privation

agitated

leading

ved and

animals

correct

table. In

nd 70%

study of

on a 1-s

study is

stable

T

studies

novelty

and pe

the sam

acute

attentio

in the 5

by prio

and loc

prior 6-

depriva

in the 5

ACKNO

The au

and An

The prese

s that show

y exposure

erformance

me sleep d

sleep dep

on. Selectiv

5-CSRTT,

or sleep de

comotor a

-h sleep d

ation does

5-CSRTT.

OWLEDGE

uthors wou

nnick Heyle

ent study u

wed no eff

e and frustr

e of anima

deprivation

privation d

ve and su

starting 1

eprivation d

ctivity leve

eprivation.

not affect

EMENTS

uld like to

en for their

used the s

fect of acu

rative non-

ls during a

n and telem

does also

stained at

.5 h after s

despite a

els during

. We there

sustained

thank Han

r technical

same expe

te sleep d

-reward str

an operant

metric met

not affec

tention, m

sleep depr

significant

the 5-CSR

efore conc

and selec

nsfried van

assistance

Sleep dep

erimental m

eprivation

ress and o

t task (Cha

hods, the

ct different

otivation a

rivation ter

t sleep def

RTT asses

lude that a

ctive attent

n Craenen

e.

privation a

methods a

on the str

n the moti

apter 4 an

present st

t compone

and impuls

rmination,

ficit. Also b

ssment we

acute gent

tion and be

ndonck, Le

and the 5-

as in our p

ress respo

vation, imp

nd 5). Whil

tudy confir

ent proces

sivity as as

were not a

body temp

ere unaffe

tle handlin

ehavioural

een Raeym

CSRTT

141

previous

onses to

pulsivity

e using

rms that

sses of

ssessed

affected

perature

cted by

g sleep

control

maekers

Chapter 7

General Discussion

Chapte

144

STRESBEHAV

In orde

studies

behavio

Koolha

part of

require

nature

studies

the sam

1992; K

system

activati

to aver

1980; B

2006; K

I

physiol

before,

novel c

on the

discuss

conside

(Weiss

absenc

though

delayed

view, w

unpred

The res

adreno

activati

er 7

SS SYSTVIOUR?

er to interp

s correctly,

our. In this

aas and co

the class

ements for

of the sit

s showing

me brain m

Koob, 199

m activatio

on. Studie

rsive stimu

Bronson a

Koolhaas e

In chapte

ogical, ho

during an

cage has b

occurrenc

sed and hy

ered truly

, 1972; Ko

ce of an a

t to be ma

d recovery

we hypoth

ictable, or

sults in ch

omedullary

on togeth

TEM AC

ret the con

this thesi

s thesis we

o-workers (

ical stress

r normal o

tuation (K

that physic

mechanism

99). This is

n occurs

es confirm

li but also

and Desjar

et al., 2011

r 2 we

rmonal, be

nd after n

been interp

ce of a str

ypothesize

stressful,

oolhaas et

anticipator

ainly chara

y of the str

esize that

possibly e

hapter 2 sh

(SAM) s

er with ex

CTIVATION

nsequence

s aimed to

e support t

(Koolhaas

s system a

ongoing be

oolhaas e

cal activity

s as stress

s describe

in any c

that the st

in respons

rdins, 1982

; Buwalda

further st

ehavioural

ovel cage

preted as a

ress respo

ed by Koolh

needs to

t al., 2011

ry respons

acterized b

ress respo

t novel ca

even not at

how that n

system an

xplorative

N AS P

es of sleep

o study str

he concep

et al., 201

activation i

ehavioural

et al., 201

y results in

sors (Axelr

ed in more

condition t

tress syste

se to positi

2; De Boe

a et al., 201

tudied the

and electr

exposure

a stressor

onse. As W

haas and c

o involve

). Unpredi

se (Koolha

y a perceiv

onse (Kool

ge exposu

t all, since

novelty exp

nd hypoth

activities a

PHYSIOLO

p deprivatio

ress syste

pt of stress

11). They s

is a direct

activity, r

1). This h

stress sys

rod and Re

e detail in

hat requir

ems are no

ve and rew

er et al., 1

12).

e concept

roencepha

e in rats. F

but this in

Weiss show

co-workers

uncontrol

ictability ca

aas et al.,

ved recept

haas et al

ure is only

cages are

posure ind

halamic-pit

and groom

OGICAL

on and the

m activatio

s that has b

suggest th

t reflection

rather than

hypothesis

stem activ

eisine, 198

the next p

res or cau

ot only activ

warding sti

1990a; Bo

of stres

alographic

Forced con

terpretatio

wed and a

s, a conditi

lability an

an be cha

2011). U

tion of loss

l., 2011). F

y mildly u

e cleaned o

duces temp

tuitary-adre

ming. Corr

SUPPOR

e outcomes

on in conc

been propo

hat a consi

of the me

n of the s

is suppo

vation via s

84; Johnso

paragraph.

uses beha

vated in re

muli (Schu

nilla-Jaime

ss by me

(EEG) res

nfrontation

n is simply

as has als

ion, in orde

d unpredi

aracterized

Uncontrolla

s of contro

From this

ncontrollab

on a weekl

poral symp

enal (HPA

relational a

RT OF

s of our

cert with

osed by

derable

etabolic

stressful

orted by

some of

on et al.,

. Stress

avioural

esponse

uurman,

e et al.,

easuring

sponses

n with a

y based

so been

er to be

ctability

by the

ability is

ol and a

point of

ble and

y basis.

pathico-

A) axis

analysis

showed

novelty

that st

behavio

physiol

the act

Wollnik

wheel

novelty

with the

that the

suppor

ongoing

stress i

D

is expe

unpred

can be

respon

hypothe

corticos

compa

(Schuu

Koolha

conside

behavio

respon

were as

for food

animal

loss of

non-rew

1990a)

d that the

y exposure

tress syste

oural activ

ogical and

tive phase

k, 1982; D

running (

y exposure

e behaviou

e physiolog

rt the beha

g behaviou

interpretati

Dissociatio

ected to o

ictability. T

distinguis

ses rather

esis is sup

sterone an

red to a co

urman, 198

aas et al., 2

erable par

our and th

se occurs

ssessed in

d reinforce

faces abs

control. S

ward stres

). We the

heart rate

e were clos

em activa

vity of the

d hormona

e of the ci

De Boer an

Boersma

was fast a

ural respon

gical and h

aviour indu

ur therefor

ion.

on betwee

occur in a

The hypoth

shed from

r than the

pported by

nd/or SAM

ontrollable

80; Garcia

2011). The

rt of stres

at dissocia

in a uncon

n an opera

ements. W

sence of t

Such unex

ss and is

erefore hy

, blood pre

sely related

ation in re

e animals.

l levels no

rcadian cy

nd van de

et al., 20

and these

nse. These

hormonal r

uced. An

re seems to

n the beh

truly stre

hesis is tha

a controlla

magnitude

y several s

M system

one, that w

a et al., 2

findings o

ss system

ation betwe

ntrollable a

nt-conditio

When lever

the expect

pected lo

highly unc

ypothesize

essure and

d to the on

esponse t

The stres

ot exceedin

ycle under

r Gugten,

011). More

recovery re

e observati

responses

interpretat

o me more

avioural a

essful situa

at an unco

able and p

e of the re

studies tha

response

was not du

2000; Fish

of chapter 5

activation

een the be

and unpred

oning task i

r pressing

ted behav

oss of cont

controllable

ed that d

d plasma c

going beha

o novelty

ss system

ng the ave

r home ca

1987) or

eover, rec

esponses

ions furthe

to novelty

tion in term

e appropria

nd physio

ation, cont

ontrollable

predictable

esponse (K

at showed

after an

ue to differe

h et al., 2

5 further su

n serves a

ehavioural

dictable sit

in which ra

is sudden

ioural con

trol has be

e and unp

dissociation

Ge

corticoster

avioural ac

is closel

m activatio

rage value

age conditi

values rel

covery upo

were also

er strengthe

exposure

ms of met

ate than th

logical/hor

taining unc

and unpre

one by th

Koolhaas e

a delayed

uncontroll

ences in be

005; Arnh

upport our

as physiolo

and physi

uation. In c

ats are train

nly no long

sequence

een descri

predictable

n between

eneral Dis

rone respo

ctivity. This

y related

n was mi

es reached

ions (Buttn

lated to vo

on termina

closely co

en our hyp

are mand

tabolic sup

he frequent

rmonal res

controllabi

edictable s

he recovery

et al., 201

d recovery

able situa

ehavioural

hold et al.

r hypothesi

ogical sup

ological/ho

chapter 5 a

ned to leve

ger reward

and expe

bed as fru

e (De Boer

n stress

scussion

145

onses to

s shows

to the

ld, with

d during

ner and

oluntary

ation of

rrelated

pothesis

atory to

pport of

tly used

sponses

lity and

situation

y of the

1). This

y of the

ation as

activity

, 2009;

is that a

pport of

ormonal

animals

er press

ded, the

eriences

ustrative

r et al.,

system

Chapte

146

activati

reward

system

during

tempor

conditio

activati

suppor

conditio

behavio

activity

conditio

reward

comple

conditio

but with

increas

showin

1971a;

1983;

dissoci

pronou

more a

remain

activati

reward

recove

and/or

control

1980; G

2011).

I

respon

er 7

on and be

ed conditi

m and HPA

the recov

ral characte

on and tha

on in resp

rt of behav

on, dissoci

oural activ

showed s

on had a

ed animal

ete the ta

ons and w

h increase

sed HPA a

g stronger

Coover e

Osborne,

ation betw

nced. Whe

and reache

ed elevate

on that m

, also refe

ry. This is

SAM sys

lable one,

Garcia et

In our ex

se but not

ehavioural

ion, which

A axis were

very of th

eristics as

at decreas

ponse to re

viour induc

iation occu

vity respo

similar temp

decreased

s. This in

sk. This r

was associ

ed corticost

axis activat

r HPA axis

et al., 1971

1986).

ween SAM

ereas the b

ed levels c

ed. There

mainly serv

rred to as

in line with

tem respo

that was n

al., 2000;

xperiment,

t for the S

activity w

h is highly

e activated

he conditio

the behav

sed during

eward can

ced by the

urred betwe

nse wher

poral chara

d behaviou

dicates th

reduced m

ated with

terone leve

tion in resp

s activation

b; Davis e

During re

system ac

behavioura

omparable

efore, we

ved as phy

frustrative

h studies s

onse after

not due to

Fish et a

we found

SAM system

would occu

y controlla

d and that

on. This s

vioural acti

the recov

be adequa

situation.

een the pla

reas SAM

acteristics.

ural activity

at these a

motivation

a concom

els as com

ponse to n

n when los

et al., 1976

ecovery of

ctivation an

al activity a

e to the rew

conclude

ysiological

non-rewa

howing a d

an uncon

difference

l., 2005; A

d a delay

m respons

ur. Our re

able and p

this stress

stress sys

vity respon

ery. Conse

ately interp

In contras

asma cortic

system a

. The anim

y during th

animals ha

was expe

mitant reduc

mpared to t

on-reward

ing behavi

6; Hart and

f the no

nd HPA ax

and SAM s

warded an

that rewa

support o

rd stress,

delayed re

ntrollable s

es in behav

Arnhold et

yed recov

se after fru

esults show

predictable

s system a

stem activa

nse that wa

equently, t

preted in te

st, during t

costerone

activation

mals under

he trial as

ad a reduc

ected und

ced SAM

the reward

is in line w

ioural cont

d Coover,

n-rewarded

is activatio

system act

nimals, cor

ard induce

of behavio

caused a d

covery of t

situation a

vioural act

al., 2009;

very for th

ustrative n

w that dur

e, both th

activation r

ation had

as induced

the stress

erms of me

the non-re

response

and beha

the non-re

compared

ced motiva

der non-re

system ac

ded conditio

with other

trol (Coove

1982; Coe

d conditio

on was eve

tivation dec

rticosterone

ed stress

our, but th

delayed H

the cortico

s compare

tivity (Schu

; Koolhaas

he cortico

on-reward

ring the

e SAM

reduced

similar

d by the

system

etabolic

ewarded

and the

avioural

ewarded

d to the

ation to

ewarded

ctivation

on. The

studies

er et al.,

e et al.,

on, the

en more

creased

e levels

system

at non-

PA axis

osterone

ed to a

uurman,

s et al.,

osterone

stress.

The me

are larg

recove

non-ge

glucoco

glucoco

though

study s

involve

binding

week a

hippoca

Anothe

sexual

by the

differen

experie

parasy

et al., 2

thirsty r

is unsu

HPA a

pathwa

differen

differen

deman

physica

associa

Cerro e

non-rew

Terman

further

adrena

echanisms

gely unkno

ry after an

enomic co

orticoid re

orticoids (D

t to play a

showed te

ed in the f

g in brain a

after social

ampus wh

er study sh

behaviour

temporal

nce in HPA

ence (Buw

mpathetic

2009). Tha

rats during

ure what in

axis respon

ays for str

nt SAM sy

nt physica

ds. Furthe

al activity,

ated with t

et al., 200

ward (De

n, 1980; C

showed th

alin levels w

s underlyin

own. For t

n uncontro

orticostero

ceptors (G

De Kloet e

n importan

emporal dy

feedback i

areas like t

defeat and

hen measu

howed no d

r or social

dynamics

A axis reco

walda et a

nervous s

at study sh

g drinking t

our study

nse during

ress-induce

ystem and

l and psy

ermore, SA

, and mo

his (Christ

3). Studie

Boer et a

Coover et a

hat the ad

were increa

ng the cha

the HPA a

llable situa

oid recep

GR) feedb

et al., 200

nt role in th

ynamics o

inhibition (

the hypoth

d that MR

ured 3 we

difference

defeat (Bu

of the MR

overy will o

al., 2012).

ystem in th

howed a r

that could

caused th

g non-rewa

ed stimula

HPA axis

ychological

AM system

ore specifi

ensen and

es have fo

al., 1990a)

al., 1984; D

drenalin res

ased toget

ange in SA

axis respon

ation is ca

tor mine

ack inhibit

8). This n

he termina

of the MR

(Buwalda

halamus an

binding wa

eks after

in the rec

uwalda et

R and GR

occur with

Another

he recover

rapid decli

be preven

e dissociat

ard. There

ation of th

s response

l processe

activation

ically, nor

d Galbo, 19

ound a red

with a hig

De Boer et

sponse dis

ther with co

AM system

nse, it is h

used by a

ralocortico

tion that i

egative fe

tion of the

R and GR

et al., 200

nd hippoca

as reduced

social defe

overy of th

al., 2012).

R distributio

a longer d

study sug

ry of the H

ne of plas

ted by sub

tion betwe

e may be

he SAM a

e by non-re

es involved

is conside

radrenalin

983; Axelro

uced eleva

gher HPA

t al., 1990a

ssociated f

orticostero

Ge

m activation

hypothesize

delayed o

oid recep

s induced

edback in

corticoste

distributio

01). They

ampus was

d by 40% i

eat (Buwa

he HPA ax

The autho

on and hy

delay after

ggests inv

PA axis re

sma cortico

bdiaphragm

een the SA

a differen

nd HPA s

eward ma

d in the a

ered close

has foun

od and Re

ation in no

axis activa

a). De Boe

from norad

ne levels d

eneral Dis

n during re

ed that a d

onset of th

ptors (MR

by the re

hibition sy

erone respo

on in brain

showed t

s decrease

in the sept

alda et al.,

xis respons

ors explain

pothesized

r the socia

volvement

esponse (A

osterone le

matic vago

M system

nce in the

system. Al

y reflect o

adaptation

ly associat

nd to be

eisine, 198

oradrenalin

ation (Bou

er and co-w

drenalin, a

during non

scussion

147

ecovery

delayed

he rapid

R) and

eleased

ystem is

onse. A

n areas

hat GR

ed one

tum and

2001).

se after

ned this

d that a

l defeat

of the

Arnhold

evels in

otomy. It

and the

e neural

lso, the

or serve

to the

ted with

closely

4; Leal-

n during

los and

workers

and that

-reward

Chapte

148

wherea

accorda

control

and ad

stayed

did not

betwee

dissoci

noradre

T

to be c

elemen

unpred

by dis

respon

also co

order t

behavio

SLEEP

This th

activati

study t

system

T

sleep d

in incr

corticos

activity

statistic

in line w

er 7

as noradre

ance with

the adren

drenalin le

elevated (

t study nor

en the HPA

ation occu

enalin redu

The results

onsidered

nts. Moreov

ictable situ

ssociation

ses and th

onfirm the

to interpre

our or in te

P DEPRIVA

hesis also

on is resp

this, we fir

ms.

The results

deprivation

reases in

sterone as

levels we

cally signif

with other

enalin leve

another s

nalin and n

evels to re

(Dobrakovo

radrenalin

A axis and

urring betw

uction may

s of chapte

truly stres

ver, these

uation can

between

hat this is r

need to s

et the resu

erms of stre

ATION AN

aimed to

ponsible fo

rstly focuse

s of chapte

induced a

body te

s compare

ere increa

ficant durin

experimen

els were

study that s

oradrenali

epeated ha

ova et al.,

and adren

d SAM sys

ween the no

y be more p

er 2 and 5

ssful, need

studies co

be disting

the beh

reflected in

study the

ults correc

ess.

ND ACTIVA

o further i

or some of

ed on the

er 3, 4 and

activation o

emperature

ed to the n

ased. Thes

ng the who

ntal rodent

reduced (

suggests t

n response

andling wh

1993). In t

nalin levels

stem respo

oradrenalin

pronounce

confirm o

s to contai

onfirm the

guished fro

havioural

n the recov

stress res

ctly in term

ATION OF

nvestigate

f the adve

effect of s

d 5 show th

of the stres

e, heart

non-depriv

se increas

ole sleep d

studies re

(De Boer

that there

e and show

hereas no

the studies

s. Possibly

onse in ou

n and adre

ed than the

ur hypothe

in uncontro

hypothesis

om a contr

and phy

very of the

sponses in

ms of me

THE BAS

e our hypo

rse conse

sleep depr

hat acute 4

ss systems

rate, bloo

ved contro

ses were

deprivation

porting mil

et al., 19

are differe

wed reduc

oradrenalin

s described

y, the disso

r experime

enalin resp

e adrenalin

esis that a

ollability an

s that an u

rollable an

ysiological/

e response

n concert w

tabolic su

SAL STRES

othesis th

quences o

rivation on

4 and 6 h o

s. Overall,

od pressu

ol condition

mild and

period. T

ld activatio

990a). Thi

ent pathwa

ced cortico

n dissociat

d in this the

ociation ob

ent is relat

ponses, wh

increase.

situation,

nd unpredi

uncontrolla

d predicta

/hormonal

es. These

with behav

pport of o

SS SYSTE

at stress

of sleep lo

n the basa

of gentle h

this was re

ure and

n. Also loc

were not

his observ

on of, in pa

is is in

ays that

osterone

ted and

esis, we

bserved

ted to a

here the

in order

ctability

able and

ble one

stress

studies

viour in

ongoing

EMS

system

oss. To

al stress

handling

eflected

plasma

comotor

always

vation is

articular,

the HP

et al., 2

S

and bo

the ligh

the nor

preced

studies

pressu

Sforza

relaxed

levels s

depriva

W

sleep d

detail,

using f

2006;

recove

the sle

stress s

and co

depriva

2002).

two da

depriva

A

the res

brain (M

activati

in the p

in the

form a

A axis (Su

2006).

Sleep depr

ody temper

ht phase, i

rmal wakin

ing sleep

s showing

re towards

et al., 200

d wakefuln

seen durin

ation (Buwa

Whereas o

deprivation

the dynam

frequent sa

Sgoifo et

ry times bu

ep depriva

systems u

-workers a

ation that

Despite fa

ays were n

ation (Sgoif

Activation

ult of comp

Meerlo et a

on simulta

paraventric

brain stem

feed-forw

uchecki et

rivation pre

rature that

.e., circad

ng levels

deprivatio

that sleep

s levels rea

04). Only

ess but th

ng mild str

alda et al.,

other rode

and have

mics of the

ampling (S

al., 2006

ut all had r

ation proce

pon acute

also showe

disappear

ast recover

needed for

fo et al., 20

of the SA

plex, recip

al., 2008).

aneously v

cular nucle

m, that tog

ward syste

al., 1998;

evented th

was obse

ian resting

as measu

on were m

p deprivatio

ached duri

plasma co

ese levels

ress and w

1993; Van

ent studies

limited da

e recovery

Suchecki e

6). Our st

returned to

edure. The

sleep dep

ed a mild H

red within

ry of the HP

r the incre

006).

M system

rocal intera

Sleep dep

via the Cor

us of the h

ether have

m involved

Meerlo et

e normal d

erved in th

g phase. L

ured during

maintained

on induced

ng normal

orticosteron

can still b

were only r

n den Buus

mainly fo

ata on the r

of the str

et al., 1998

udies sho

o control le

e data pre

privation ha

HPA axis a

a few ho

PA axis in

eased hear

and the H

actions be

privation ca

rticotrophin

hypothalam

e strong re

d in arous

al., 2002;

decline in l

e control s

evels com

g the last

d. This is

d an increa

wakefulne

ne reache

be conside

reached du

se et al., 2

ocused on

recovery, t

ress respo

8; Meerlo e

ow that th

evels within

esented ind

as tempora

activation i

ours after

that study

rt rate to r

HPA axis b

tween diffe

an induce

n-Releasin

mus and via

eciprocal s

sal and st

Ge

Hipolide et

ocomotor

situation at

mparable to

30 min o

in accord

ase in hea

ess (Tochi

d higher le

red low as

uring the f

2001; Such

the stress

this thesis

onse after

et al., 200

e respons

n 45 min a

dicate that

al effects. A

n response

terminatio

y, another s

recover af

by sleep de

erent arous

SAM syst

ng-Hormon

a noradren

stimulatory

ress (Axel

eneral Dis

t al., 2006

activity, he

t the begin

o or slightly

f the dark

dance wit

art rate an

kubo et al

evels than

s they were

first hour o

hecki et al.,

s response

aimed to s

sleep dep

02; Hipolide

ses had d

fter termin

t activation

A study by

e to 48 h o

on (Meerlo

study show

fter 48 h o

eprivation

sal system

em and H

ne (CRH) n

nergic cell c

y interactio

lrod and R

scussion

149

; Sgoifo

eart rate

nning of

y below

k period

h other

d blood

., 1996;

n during

e below

of sleep

, 2002).

e during

show, in

privation

e et al.,

different

nation of

n of the

y Meerlo

of sleep

o et al.,

wed that

of sleep

is likely

ms in the

PA axis

neurons

clusters

ons and

Reisine,

Chapte

150

1984;

noradre

system

not onl

also a

stress

behavio

activati

stressfu

arousa

2012).

during

et al., 1

higher

studies

Zhong

input fr

during

produc

orexin

clusters

and by

Samso

Brown

is the r

2012).

sleep o

Moreov

cognitiv

arousa

arousa

A

or 6 h a

er 7

Johnson e

energic ce

m, is though

y act as n

regulator

(Chang a

oural activ

on. The n

ul conditio

l (Grzanna

During wa

sleep. The

1994). High

firing rate

s where su

et al., 200

rom other s

sleep dep

ed by neu

neurons s

s in the bra

y that way

on and Re

et al., 201

regulation

Orexin ne

or relaxed

ver, as rev

ve and ph

l and prom

l and cogn

Altogether

affects the

et al., 199

ll clusters

ht to be, at

eurotransm

of wakefu

and Opp,

vity, eithe

noradrener

ons, but a

a and Frits

aking, incre

ese firing ra

her SAM s

es of the n

ubjects are

05). The C

systems th

rivation. Th

urons loca

send proje

ainstem w

stimulate

esch, 2000

2). The or

of sleep a

eurons sho

wakefulne

viewed by

hysical aro

moting SA

nitive functi

, our studie

basal acti

92; Koob,

during stre

t least part

mitter invol

ulness and

2001). By

r stressfu

rgic cell cl

also play a

schy, 1991

eases in fi

ates are as

system and

noradrene

e involved

CRH neuro

hat may co

he orexin (

ated in the

ections to

where they

SAM syst

0; Sutcliffe

rexin syste

and arous

ow activity

ess (Kiyash

Meerlo an

ousal the

AM system

ioning (Me

es show th

ivity of the

1999; Br

ess, resulti

tly, depend

lved in aro

d spontane

y these m

l or unstr

lusters are

a major ro

; Berridge

ring rates

ssociated w

d HPA axis

rgic cell c

in menta

ons and no

ntribute to

(also know

e lateral hy

the hypot

can affect

tem and H

and de,

m has mu

al states (

y during a

hchenko et

nd co-work

orexin sys

and HPA

eerlo et al.,

hat acute g

stress sys

rown et al

ng in outp

dent on CR

ousal unde

eous beha

mechanism

ressful, ca

e not only

ole in fore

and Wate

have been

with arous

s activation

clusters, is

al challeng

oradrenerg

HPA axis

wn as hypo

ypothalam

thalamus

CRH rele

HPA axis a

2002; Fer

ltiple funct

(Sutcliffe a

active waki

t al., 2002

kers, when

stem may

A axis activ

2008) .

gentle han

stems mild

l., 2012).

ut of the a

RH (Koob,

er stressful

aviour in c

ms, any co

an result

y involved

ebrain act

erhouse, 20

n observed

al and atte

n, thought

s seen in

es (Radom

gic cell clus

and SAM

ocretin) sys

us, is suc

and the n

ase and a

activity (Pe

rguson and

tions and o

and de, 20

ing as com

; Mileykov

n waking i

play a ro

vity neede

dling sleep

ly and tem

Activation

utonomic n

1999). CR

conditions

conditions

ondition re

in stress

in arousa

tivation an

003; Brow

d as comp

ention (ston

to be the r

sleep dep

mski et al.

sters also

system ac

stem, with

ch a syste

noradrener

utonomic f

eyron et al

d Samson

one import

000; Brown

mpared to

vskiy et al.

s associat

ole in main

ed to supp

p deprivatio

mporarily. D

of the

nervous

RH does

s, but is

without

equiring

system

al under

nd EEG

n et al.,

pared to

n-Jones

result of

privation

., 1992;

receive

ctivation

orexins

em. The

rgic cell

function

., 1998;

n, 2003;

tant role

n et al.,

o during

, 2005).

ted with

ntaining

port this

on for 4

Different

brain m

depriva

and the

Stress

wakefu

Therefo

what ex

by acut

CONSE

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the 1.5 h re

sleep EEG

scussion

151

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152

power

1979;

observe

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confirm

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stress s

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method

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experim

conside

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1993).

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1998). Thi

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ild proced

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, 2010). In

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al., 1995;

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scussion

153

synaptic

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system

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, 2008).

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20 h of s

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8 days

n in the

ersisted

y forced

06). The

reduce

may, a

been o

Interes

to CRH

agonist

2002).

restricte

Roman

or restr

what

neurotr

A

stress

signific

from th

animals

comple

depriva

sleep t

reboun

et al.,

Therefo

likely, 4

able to

and str

related

activati

chronic

immed

deprive

depriva

d CRH se

at least pa

observed

tingly, dep

H injections

t (Holsboe

This is s

ed of slee

n et al., 200

riction can

is seen

ransmitter

Altogether

responsivi

ant sleep

his sleep d

s lost half

ete recove

ation, a co

that was lo

d observe

1989a; Ev

ore, anima

4 and 6 h o

recover co

ress system

to acute

on occurri

c sleep d

iately but

ed sleep

ation durat

nsitivity an

rtly, accou

in studies

pressed pa

s, and they

er et al., 19

similar to

ep (Meerlo

06; Novati

cause gra

in depre

systems in

, our studi

ty to nove

deficit indu

deficit. Sinc

of their sl

ery in thi

omplete re

ost. Chron

d does no

verson et

als may no

of sleep de

ompletely.

m regulatio

sleep de

ng during

eprivation.

may grad

(Meerlo e

tion, using

nd reduced

unt for the

s using ch

atients sho

y show blu

987; Lesch

what has

o et al., 2

et al., 200

adual chan

ession. C

nvolved in

es show t

elty exposu

uced, anim

ce rats no

eep (Borb

s thesis

ecovery is

nic sleep d

ot contain a

al., 1989b

ot complete

eprivation in

We also h

on are affe

eprivation,

sleep depr

. Changes

ually deve

et al., 20

the same

d sensitivity

altered H

hronic slee

ow blunted

unted phys

h, 1991; A

been obs

002; Rom

08). This su

nges in the

hronic sle

stress syst

hat 4 and

ure and fru

mals were m

ormally slee

bely and N

but studie

initiated a

deprivation

as much N

b; Everson

ely recover

nduced a s

hypothesiz

ected, but t

with acut

rivation its

s in stres

elop under

08). We

e sleep de

y of the se

HPA axis r

ep restrict

ACTH bu

siological r

Arborelius e

served in

an et al.,

uggests th

e CRH and

eep depr

tem regula

6 h of slee

ustrative no

most likely

ep approx

euhaus, 1

es sugge

and anima

also indu

NREM slee

n, 1995; R

r from chro

significant

ze that brai

that this is

te and mi

elf, and no

ss respons

r condition

therefore

eprivation

Ge

erotonin-1A

response t

tion (Meer

ut normal c

esponses

et al., 1999

rats that

2005; Sg

hat chronic

d serotoner

rivation m

ation as we

ep depriva

on-reward

y able to co

ximately 12

979). We

st that a

als make u

uces recov

ep as that w

Rechtschaf

onic sleep

sleep loss

in systems

s associate

ild SAM s

ot with the

sivity may

ns of chron

expect th

method, w

eneral Dis

A receptor

to stress t

rlo et al.,

cortisol res

to a seroto

9; Sobcza

were chr

goifo et al.

sleep dep

rgic system

may affect

ell.

ation do no

stress. De

ompletely

2 h each d

did not st

after acute

up for the

very but th

was lost (E

ffen et al.,

deprivatio

but anima

s involved i

ed with the

system an

effects se

y not be

nic restrict

hat longe

will cause

scussion

157

system

hat has

2008).

sponses

onin-1A

k et al.,

ronically

., 2006;

privation

m, up to

t other

ot affect

espite a

recover

day, the

udy the

e sleep

NREM

e sleep

Everson

1999).

on. Most

als were

in sleep

e effects

nd HPA

en after

evident

ted and

r sleep

gradual

Chapte

158

change

and fru

SLEEP

While o

system

with an

stress

underly

attentio

1999; D

rat stu

allowed

et al., 2

I

affect

depriva

press a

motivat

sleep d

measu

corticos

termina

affect s

time ta

presen

and im

depriva

in the

compa

increas

er 7

es in the b

strative no

P DEPRIVA

our studies

m reactivity

n attentiona

systems. S

ying mech

on (Norton

Durmer an

dies that

d for separ

2006).

In chapter

attentional

ation termin

a lever to r

tion and im

deprivation

red by

sterone lev

ation of the

selective a

ask (5-CSR

ted random

pulsivity w

ation on pe

control an

red to bas

se the am

brain that m

on-reward s

ATION AN

s show tha

to challen

al challeng

Studies su

anisms of

n, 1970; H

d Dinges,

assessed

rate differe

5 we sho

l functionin

nation. Thi

retrieve a f

mpulsivity

n did not

body tem

vels and d

e task. Ch

nd sustain

RTT). In th

mly in one

were not af

erseveratio

nimals that

seline, du

mount of p

may affect

stress.

ND ATTENT

at there is

nges, we w

ge would b

uggest tha

f attention

Horne, 198

2005; Cor

sleep-dep

ent attentio

owed that 6

ng in an

is operant

food rewar

were not

affect the

mperature,

id also not

hapter 6 s

ned attentio

he 5-CSRT

of 5 holes

ffected by

on was obs

t decrease

e to unkn

erseveratio

stress sys

TIONAL F

s no effect

were still i

be affected

at sleep de

and affec

88; Wimme

rdova et al.

prived rats

onal measu

6 h of gen

operant ta

task involv

rd. During

affected b

stress re

blood p

t affect the

hows that

onal perfor

TT, rats de

s in order t

prior slee

served but

ed their am

nown reas

on when

stem respo

FUNCTION

of acute

interested

d and whe

eprivation

cts differen

er et al., 1

., 2006). T

s in a be

urements (

ntle handlin

ask as m

ved a para

the reward

by prior sl

esponse d

pressure,

e recovery

acute sle

rmance in

etect and

to get a fo

p deprivat

t this was

mount of p

on. The s

compared

onsivity to

NING

sleep dep

to see if t

ther this is

has differe

nt compon

1992; Har

here are o

ehavioural

Godoi et a

ng sleep d

measured 1

adigm whe

ded condit

eep depriv

uring the

heart ra

of the stre

eep depriva

the 5-cho

respond to

ood reward

ion. An eff

mainly cau

perseverat

sleep-depr

to baseli

novelty ex

rivation on

the ability

s mediated

ent effects

nent proce

rrison and

only few co

assessme

al., 2005; C

eprivation

1.5 h afte

ere animals

tion, perfor

vation. Mo

operant ta

ate and

ess respon

ation did a

ice serial r

o a light s

d. Also, mo

fect of prio

used by a

ive respon

rived rats

ne but did

xposure

n stress

to deal

d by the

on the

sses of

Horne,

ontrolled

ent that

Cordova

did not

er sleep

s had to

rmance,

oreover,

ask, as

plasma

se after

also not

reaction

stimulus

otivation

or sleep

change

nses as

did not

d when

compa

rats sh

showed

the no

reporte

depriva

respon

been a

been in

would b

have c

selectiv

et al., 2

behavio

Th

outcom

CSRTT

depriva

depriva

essenti

further

sleep d

2006).

used s

tactile s

handlin

depriva

activati

(Dobra

mediate

4, 7 an

correct

of slee

red to cont

owed a str

d a small d

n-deprived

ed in a p

ation; but a

ses was n

attributed t

nitiated. W

be interest

combined

ve and sus

2006) and

oural contr

here are s

mes among

T after slee

ation durat

ation where

ial differen

compare

deprivation

They use

sensory, a

stimulation

ng proced

ation. Habi

on cause

kovova et

ed in part

nd 10 h of t

t responses

p deprivat

trol conditi

rong increa

decrease i

d rats. Ind

previous s

a significan

not found

o a compu

We were un

ting to stud

sleep dep

stained atte

96 h of RE

rol.

several me

g our study

ep deprivat

tion play a

eas we us

nce may a

that study

n method

ed the gen

auditory an

n (Cordova

ures that

tuation to

ed by the

al., 1993

by the str

total sleep

s during sl

tion. In my

ons. Also,

ase in som

n the amo

dividual va

study on

nt overall e

in that stu

ulsive inab

nable to m

dy these du

privation w

entional de

EM sleep d

ethodologic

y and the tw

tion. Differ

a role. Go

sed 6-h to

account fo

with ours

and durat

ntle handlin

nd tactile

a et al., 200

were use

handling w

e gentle

). This ma

ress system

p deprivatio

eep depriv

y opinion, t

analysis o

me rats, wh

ount of per

ariability in

5-CSRTT

effect of s

udy (Cord

bility to dis

easure str

uring a nex

with subseq

eficits after

deprivation

cal aspect

wo other s

rences in s

odoi and c

otal sleep d

or the diffe

. The stud

tion more

ng sleep d

stimulation

06). Also, w

ed to kee

will reduce

handling

ay also re

ms, on atte

on and fou

vation and

there is a

of individua

hereas othe

severative

n persever

performa

leep depri

ova et al.

sengage fr

ress read-o

xt study. T

quent 5-CS

r 10-h total

n (Godoi et

ts that cou

tudies that

sleep depri

co-workers

deprivation

erent outco

dy of Cordo

comparab

deprivation

n whereas

we habitua

ep the an

the extent

used to

educe the

ention. Co

nd an incr

a positive

possibility

Ge

al data of th

ers remain

response

rative resp

nce follow

vation on

, 2006). P

rom respon

outs during

he two oth

SRTT ass

sleep dep

t al., 2005)

uld accoun

t assessed

ivation pro

s used 96

n (Godoi e

omes and

ova and c

ble to ours

n method,

s our proc

ated the an

imals awa

t of HPA a

keep the

effect of s

rdova and

rease in re

interaction

that this i

eneral Dis

he sleep-d

ned stable

s as comp

ponses wa

wing 10 h

the persev

Perseveran

nding once

g the 5-CS

her rat stud

sessment s

privation (C

) but no eff

nt for the d

d animals i

ocedure an

h of REM

et al., 2005

make it

o-workers

s (Cordova

but their

cedure use

imals to th

ake during

axis and ad

animals

sleep depr

co-worke

sponse lat

n with the d

interaction

scussion

159

deprived

or even

pared to

as also

h sleep

verative

nce has

e it has

SRTT. It

dies that

showed

Cordova

fects on

different

n the 5-

nd sleep

M sleep

5). This

hard to

used a

a et al.,

method

ed only

he same

g sleep

drenalin

awake

rivation,

rs used

tency to

duration

is also

Chapte

160

caused

sleep d

experim

were a

towards

despite

for mor

state a

sustain

depriva

behavio

increas

result o

should

confou

agitatio

develop

missing

process

studies

compa

subseq

howeve

perform

S

loss re

prefron

disrupt

cortex

sleep d

occur

forebra

adminis

er 7

d by an acc

deprivation

ment we fu

ssessed in

s the end

e the 1.5-h

re than 30

nymore wh

ned and s

ation studi

oural state

sed agitatio

of sleep lo

include a

nding effe

on. Further

ped and u

g, possibly

ses involv

s. In our s

red to the

quent 5-C

er still ab

mance befo

Studies su

flect mainl

ntal cortex

ions of the

(Muir et al

deprivation

during wa

ain (Hawryl

stration in

cumulating

n subsequ

urthermore

n the atten

of the sl

recovery o

0 min after

hen asses

selective a

ies are th

e. A study

on (Corriga

oss or of t

recovery ti

cts. Also,

rmore, a s

sed amon

y leading to

ved and m

study, rats

e other ra

SRTT ass

bove the

ore they we

uggest tha

ly a dysreg

(Norton, 1

e basal fo

l., 1992; M

n is though

akefulness

luk et al., 2

the basal

g sleep dep

uently with

e included

tional task

eep depriv

of sleep de

r terminatio

sed in the

attentional

he result

showed th

an et al., 1

the sleep d

ime before

future stud

standardize

g studies.

o a differen

maximum

reached

at studies

sessment.

chance le

ere sleep-d

at the atten

gulation of

970; Durm

rebrain ch

McGaughy

ht to be th

and that

2012; Brow

forebrain

pth as the

h only one

a post-de

k. As discus

vation ses

eprivation p

on of the 5

5-CSRTT

deficits f

of animals

hat attentio

1992). Sinc

deprivation

e exposing

dies are n

ed training

In most a

nce in acqu

stable pe

a 20% low

s that hav

The per

evel of 2

deprived.

ntional def

f behaviou

mer and Di

holinergic f

et al., 200

he result o

t inhibit th

wn et al., 2

results in

rats were

e day in b

eprivation r

ssed previ

ssion. In c

period, ani

5-CSRTT

. This raise

found in

s being in

onal deficit

ce it is unk

n procedur

rats to an

eeded to d

protocol f

articles, de

uiring the t

erformance

wer perfor

ve combin

rformance

20% and

ficits comm

ural control

nges, 200

function, th

02; Brown

of increase

he choline

2012). A st

sustained

exposed to

between to

recovery p

ously, rats

chapter 6

imals still h

but were n

es the que

experimen

n a differ

ts are high

known if th

re, we sug

attentiona

determine

for the 5-C

etailed train

ask, differe

e reached

rmance in

ned sleep

reached

all anima

monly obs

l processe

5), and mo

hat project

et al., 201

es in aden

ergic neuro

tudy showe

d attention

o 4, 7 and

o recover.

period befo

s became a

we showe

had a sleep

not in an a

estion whet

ntal roden

rent emoti

hly correlat

his agitatio

ggest that

al task to m

the cause

CSRTT sh

ning protoc

ences in co

across d

the 5-CSR

deprivatio

in our s

als had a

served afte

es that rely

ore specific

t to the pr

2). This e

nosine lev

ons in the

ed that ade

impairme

10 h of

In our

ore rats

agitated

ed that,

p deficit

agitated

ther the

t sleep

onal or

ted with

n is the

studies

minimize

e of this

ould be

cols are

ognitive

different

RTT as

on with

study is

stable

er sleep

y on the

cally, of

refrontal

effect of

els that

e basal

enosine

nts that

were m

Studies

to an i

al., 20

system

attentio

attentio

be invo

attentio

The m

glucoco

induce

axis an

1987;

cortex

prefron

Srikum

discuss

waking

Waterh

attentio

change

perform

1989;

catecho

cortex

Arnsten

activati

perform

the att

depriva

Fratta,

are, in

mimicking t

s also show

ncrease in

03). In th

ms. We did

onal functi

onal perfor

olved. Inte

onal functio

medial pref

orticoids o

acetylcho

nd on the c

Brown et

and cause

ntal cortex

ar et al., 2

sed, the n

as comp

house, 200

onal perfor

e the regul

mance, but

Meerlo e

olamines a

may wea

n, 2008). S

on and by

mance by t

entional d

ation result

1997). Th

part, invol

he effects

wed that c

n persever

is thesis

d not find a

oning and

rmance is a

erestingly,

oning, but

frontal co

on HPA ax

line releas

cholinergic

al., 2012)

es a gradu

mediated

2006). The

noradrener

pared to d

03; Brown

rmance (st

ation of th

t there is l

et al., 20

and too lit

aken cogn

Since slee

y that way

this mecha

eficits com

ts in reduce

is may als

ved in atte

seen after

cholinergic

rative resp

we focuse

an effect o

d on beha

affected by

the media

also affec

rtex is a

xis activity

se in the h

function o

. Chronic

al decline

behaviou

noradrene

rgic cell c

uring slee

et al., 20

ton-Jones

e noradren

ittle and c

08). The

ttle or too

nitive contr

p deprivat

results in

anism as w

mmonly ob

ed CRH se

so occur in

entional pro

r 24 h of sl

disruption

ponses (Mc

ed on the

of sleep de

avioural co

y sleep dep

al prefronta

cts activity

target fo

y. Acute ac

hippocamp

of the prefr

stress sys

of choline

urs, such a

ergic cell c

clusters sh

ep (Grzann

012) and t

et al., 199

nergic syst

controversia

prefronta

much cat

rol of beh

tion is in g

catecholam

well. The C

bserved af

ensitivity in

n the prefro

ocesses (J

eep depriv

s in the m

cGaughy e

e possible

eprivation

ontrol, but

privation, t

al cortex d

of the HP

or the neg

ctivation o

us and for

rontal corte

stem activ

rgic functio

as attentio

clusters ma

how increa

na and Fr

this is tho

94). Prolon

tem and b

al evidenc

l cortex

techolamin

haviour an

general ass

mine relea

CRH syste

fter sleep

n the striatu

ontal corte

Jaferi and

Ge

vation (Chr

edial fronta

et al., 2002

involveme

on sustain

studies d

he stress s

does not o

PA axis (Di

gative fee

of the stres

rebrain tha

ex (Gilad,

vation affe

oning, resu

on (Mizogu

ay also be

ases in fi

ritschy, 19

ught to be

nged sleep

y that way

ce for this

is also v

ne release

nd attentio

sociated w

ase, it may

em may al

deprivatio

um and pit

x where th

Bhatnagar

eneral Dis

ristie et al.

al cortex c

2; Chudas

ent of the

ned and s

o suggest

systems m

only play a

iorio et al.,

edback eff

ss respon

at act on th

1987; Gila

cts the pr

ulting in de

uchi et al.

involved.

ring rates

91; Berrid

e associat

p deprivati

y affect atte

(Bergmann

very sens

e in the pr

on (Brenn

with stress

y affect atte

lso be invo

on. Chroni

tuitary (Fad

he CRH re

r, 2007). T

scussion

161

, 2008).

can lead

sama et

e stress

elective

t that if

may also

a role in

, 1993).

fects of

se may

he HPA

d et al.,

refrontal

eficits of

., 2001;

As was

during

dge and

ted with

on may

entional

n et al.,

itive to

refrontal

an and

system

entional

olved in

c sleep

dda and

eceptors

This has

Chapte

162

been s

have a

2003).

of the s

O

sleep d

activati

involve

attentio

sleep d

were m

same m

CONCL

This th

sleep d

respon

confou

depriva

attentio

system

but als

thesis

differen

the use

T

induces

the be

confirm

interpre

stress

er 7

supported

a mild accu

The norad

stress resp

Overall, th

deprivation

on. Sleep

ed in attent

on, stress

deprivation

minimized.

methods, a

LUDING R

esis descr

deprivation

se, on stre

nded cond

ation, by a

onal perfor

m activity in

o a conse

confirm th

nt attention

ed procedu

The data

s mild and

ehavioural

ms the nee

et the cons

system ac

by a stud

uracy impa

drenergic c

ponse.

e reduced

n may be t

loss and

tional proc

system an

n on atten

We expe

after more

REMARKS

ribes a ser

n to study t

ess respon

ditions. The

acting on

mance. On

n rodents is

quence of

hat our an

nal parame

ures are m

presented

d temporar

activity le

d to study

sequences

ctivation in

y that sho

airment in

cell clusters

d attentiona

the results

stress sys

cesses. Th

nd sleep p

tional perf

ct that att

prolonged

S AND FUT

ries of exp

the conseq

nsivity and

e backgrou

the stress

ne concern

s that this

f the proce

nimal mod

eters to be

inimized.

in this th

ry stress s

evels indu

the stress

s of stress

response

owed that

a version

s and the C

al performa

of sleep l

stem activa

ere is a co

rocesses.

formance

tentional d

sleep dep

TURE PER

periments t

quences of

on attentio

und of thes

s systems

n about the

may not b

edures use

del allows

e measure

hesis demo

system act

ced to ke

s response

system ac

to novelty

transgenic

of the 5-

CRH syste

ance that i

oss per se

ation both

onsiderable

In our exp

was found

deficits will

rivation.

RSPECTIV

that applied

f insufficien

onal functio

se studies

, may affe

e effects of

e a conse

ed. The ex

for multip

ed while co

onstrate th

ivation tha

eep the a

e in concer

ctivation co

y exposure

c mice ove

CSRTT (v

m are also

is common

e, but also

affect mec

e neurobio

periments,

d while co

become

VES

d an anim

nt sleep on

oning unde

is the hyp

ect stress

f sleep dep

quence of

xperiments

ple stress

onfounding

hat acute

at is closel

nimals aw

rt with beh

orrectly. O

e and acut

erproducin

van Gaalen

o activated

nly observe

o of stress

chanisms t

ological ov

no effect

onfounding

visible, us

al model o

n the basa

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dat ontho

activatie.

tie van de

en voor he

tivatie hee

e studies

effecten v

emen. De e

reactivite

dat slaap

essrespon

s ook de a

udies ten

at we st

fysiologis

N

menv

ar dat slaa

leven aan

energieba

oriek. Teve

en. In de h

ort aan sla

ar ook ee

n gezondh

s onbeken

van een

én daarvan

ouding va

Om die re

stresssyst

t organism

eft echter o

beschreve

van acute s

effecten va

eit en a

pdeprivatie

s tijdens s

aandachtsc

opzichte v

tress vers

sche, ge

Nederland

vattin

ap belangri

n slapen be

alans, tem

ens beïnvl

huidige sam

aap, waar

n verstorin

heidsprobl

nd, ook d

slaaptekor

n suggere

an slaap

eden word

temen zor

me om met

ongunstige

en in dit p

slaapdepri

an acute s

aandachtsc

e een eff

situaties d

concentrati

van de hui

storende

dragsmatig

dse samen

ng

ijk is, blijkt

esteden. S

peratuurre

oedt slaap

menleving

rbij niet all

ng van sla

emen tot

de mecha

rt zijn onb

ert betrokk

(slaapdep

dt slaapde

rgt voor ee

t de situatie

e effecten

proefschrift

vatie bij ra

slaapdepriv

concentrat

fect heeft

die stresss

ie. De me

idige verza

factoren

ge en

vatting

181

t uit het

Slaap is

egulatie,

p onder

hebben

leen de

aap een

gevolg.

anismen

bekend.

kenheid

privatie)

eprivatie

en scala

e om te

en kan

t ligt de

atten en

vatie op

ie zijn

op de

systeem

er – en

ameling

hebben

elektro-

Nederl

182

encefa

bewege

analyse

DEFIN

Om de

eerst b

situatie

stresss

gebeur

gaat m

activati

hypofys

vrijkom

verantw

en zuu

zorgt v

dieren)

energie

activati

nodig is

niet pe

gebase

aan twe

voor he

door di

analyse

I

werden

thuisko

deze s

landse sam

lografische

ende diere

es te doen

ITIE VAN

e resultate

bezig geho

e als stre

systemen t

rt niet allee

met gedra

e van het

se-bijnier-a

men van

woordelijk

rstof naar

oor het vri

), die ook e

e balans.

e die optre

s voor het

er se van d

eerd op he

ee criteria

et organism

ieren bloot

eren same

In hoofdstu

n ratten ge

ooi, maar d

situatie ve

menvatting

e (EEG) pa

en werden

die belang

STRESS

n van onz

ouden met

essvol beo

tot gevolg

en tijdens s

agsmatige

sympathic

as (HPA-a

adrenaline

zijn voor h

de spieren

ijkomen va

een rol sp

Onze hyp

eedt tijdens

gedrag wa

de mate w

et idee dat

; de situati

me. In hoo

t te stellen

en met de m

uk 2 hebb

durende v

dan zonder

eelal besc

g

arameters

n gemeten

grijk zijn vo

ze studies

t de defin

oordeeld

heeft. Ech

stressvolle

activiteit.

co-adrenom

as). Activ

e en nor

het mobilis

n door toen

an glucoco

pelen bij he

pothese is

s een bepa

at gaande

waarin de s

t een daad

ie dient zo

fdstuk 2 en

n aan twee

mate van a

en we ratt

ijftien minu

r water, voe

chreven a

simultaan

. Dit gaf t

oor het cor

juist te k

itie van st

wanneer

hter, activa

e situaties

De fysio

medullair (

vatie van

adrenaline

eren van e

name in blo

orticoïden (

et leveren

s daarom

aalde situa

is, en dus

situatie av

dwerkelijke

owel onvoo

n 5 hebbe

e verschille

activiteit va

ten bloot g

uten in een

edsel en b

ls een st

, frequent

tevens de

rrect interp

unnen inte

tress. Ove

het activa

atie van de

maar tijde

ologische

(SAM) sys

het SAM

e in het

energie eff

oeddruk e

(cortisol in

van energ

dat een

atie, een re

van de ve

versief of n

e stressvo

orspelbaar

n we de hy

ende situa

an de diere

gesteld aan

n lege kooi

bodembede

tressor om

en voor la

mogelijkh

preteren va

erpreteren

er het alge

atie van

eze fysiolo

ns elke sit

stressresp

steem en d

M-systeem

bloed die

ficiënt trans

n hartslag.

mensen e

gie en het

deel van

eflectie is v

reiste meta

negatief is

lle situatie

als oncon

ypothese v

ties en de

en.

n ‘novelty

geplaatst

ekking. In d

mdat het

angere duu

heid om co

an de resul

, hebben

emeen wo

de fysiolo

ogische sy

tuatie die g

pons best

de hypotha

zorgt vo

e onder

sport van g

. HPA-as a

en corticos

reguleren

de fysiolo

van de ene

abole activ

. De proev

e dient te v

troleerbaa

verder ond

e stressres

exposure’

, identiek a

de literatuu

activatie v

ur in vrij

orrelatie

taten.

we ons

ordt een

ogische

ystemen

gepaard

taat uit

alamus-

oor het

andere

glucose

activatie

teron in

van de

ogische

ergie die

viteit, en

ven zijn

voldoen

ar te zijn

derzocht

pons te

. Hierbij

aan hun

ur wordt

van de

stresss

oncont

inderda

exposu

van ge

‘novelty

comple

dieren

gemete

reflectie

geïndu

negatie

voldoet

van ee

waren

lichaam

factore

I

een vo

dit goe

reward

beloond

resultat

en we

geasso

fysiolog

de vere

beloond

in ged

gedure

motivat

activite

gedrag

systemen t

roleerbare

aad een h

ure’, maar d

dragsmatig

y exposure

eet herstel

geen stres

en hormon

e is van d

ceerd doo

ef is. Dus,

t deze situ

n stressor

om op

mstempera

n succesv

In hoofdstu

oedselbelon

ed is aang

stress’ te

d (extinctie

ten laten z

el een vo

ocieerd is m

gische en

eiste meta

d werden,

ragsmatige

ende de de

tie. Deze a

eit terwijl d

smatige a

ot gevolg h

en onvoo

hormonale

dat de acti

ge activite

e’ zichtbaa

na beëind

ss gerelate

nale en fys

de vereiste

or de situa

ondanks

atie, op ba

r. Deze ee

hoge fre

atuur, activ

ol gereduc

uk 5 werde

ning. Dit is

eleerd, ka

induceren

e). Dit gee

zien dat wa

oedselbelo

met de mat

hormonale

abole activ

was er oo

e activiteit

ertig minute

afname in

de cortico

activiteit en

heeft. Naa

orspelbare

en fysiolo

ivatie van d

it van de d

ar. De stre

diging van

eerd gedra

siologische

e metabol

atie en nie

dat ‘nove

asis van on

rste studie

equentie s

viteit, gedra

ceerd werd

en de diere

s een zog

an het geb

; het drukk

eft een onv

anneer het

oning krijg

te van ged

e respons

viteit. Wan

ok stresssy

t. De mat

en van de t

activiteit g

osteron sp

n HPA-as

r onze me

elemente

ogische st

de stresss

dieren. De

esssysteem

n de ‘nove

ag. Deze r

respons a

e activiteit

et van de

elty exposu

nze meting

e gaf ons t

simultaan

ag en EEG

den.

en getraind

genaamde

bruikt word

ken op het

voorspelba

t dier gedu

gt, er str

dragsmatig

lijkt in dez

nneer de d

ysteem act

e van ged

taak. De d

ging gepaa

piegels ho

activatie w

N

ening bevat

en. Onze r

ressrespon

ystemen n

ze correlat

m activatie

elty exposu

resultaten

als gevolg

t voor het

mate wa

ure’ leidt t

gen en onz

tevens de

corticoste

G te mete

d om op ee

‘operant-c

den om zo

t pedaaltje

re en onco

urende der

resssystee

e activiteit

e situatie d

dieren ged

ivatie zicht

dragsmatig

ieren werd

ard met ee

og bleven

was nog d

Nederland

t deze situ

resultaten

ns optreed

nauw corre

tie was zo

was mild

ure’. Teven

tezamen t

van ‘nove

t normale

arin de si

tot stresss

ze visie, nie

bevestigin

eron, hart

n terwijl s

en pedaaltj

conditionin

ogenaamde

wordt dan

ontroleerba

rtig minute

em activa

van de die

dus een re

durende de

tbaar, even

ge activite

den niet be

en afname

n. Deze d

duidelijker

dse samen

atie echter

laten zien

dt tijdens

eleert met d

owel tijdens

met een

ns vertoon

tonen aan

elty exposu

gedrag da

tuatie ave

systeem a

et aan de d

ng dat we

tslag, blo

tress vers

je te drukk

g taak’. W

e ‘frustrativ

n ineens ni

are situatie

n de taak

tie optree

eren. De g

eflectie te z

ertig minut

nals een to

eit nam ec

eloond en v

e in SAM-s

dissociatie

zichtbaar

vatting

183

r weinig

n dat er

‘novelty

de mate

s als na

snel en

nden de

n dat de

ure’ een

at werd

ersief of

ctivatie,

definitie

in staat

oeddruk,

torende

ken voor

Wanneer

ve non-

et meer

e. Onze

uitvoert

edt die

emeten

zijn van

ten niet

oename

chter af

verloren

systeem

tussen

na het

Nederl

184

beëind

respon

dieren.

stressv

stresss

onvoor

B

hormon

stresss

termen

SLAAP

Studies

eenduid

maar e

slaapde

slaapde

activati

gedrag

is van

activati

mentaa

effecte

3, 4 en

ratten n

derde

handlin

aaien o

dieren

hebben

method

landse sam

igen van

s die niet

Deze b

volle situat

systeem ac

rspelbaarhe

Beide stu

nale respo

systeem ac

van meta

PDEPRIVA

s naar de

dige result

er zijn ook s

eprivatie. D

eprivatie m

e voor e

smatige a

invloed op

e gezien

al actief zij

n kunnen

n 5 hebben

normaal on

tot de he

ng’ slaapde

of, als dit

werden v

n we gepro

de weinig m

menvatting

de taak. D

geassocie

evindingen

tie wordt

ctivatie en

eid.

dies tone

ons samen

ctivatie co

bole onder

ATIE EN D

effecten

taten zien.

studies die

Deze versc

methode.

een groot

ctiviteit va

p de stres

wanneer

n of wann

ook ontsta

n we ratte

ngeveer 12

elft geredu

eprivatie m

niet meer

van te vor

obeerd zo

mentale en

g

Dit wijst o

eerd is me

n versterk

gekenmer

gedragsm

n aan da

n met de

rrect te ku

rsteuning v

E STRESS

van een

. Veel stud

e geen effe

chillen zou

In hoofdst

t deel af

n de diere

sssysteem

organisme

eer de sla

aan door v

n blootges

2 uur per d

uceerd. Di

methode. D

r voldoend

ren hieraa

weinig mo

n fysieke a

op een ve

et de mate

ken onze

rkt door e

atige activ

at het be

gedragsm

unnen inte

van gedrag

SSYSTEM

slaaptekor

dies tonen

ect of zelfs

uden veroo

tuk 2 en

fhankelijk

en. Ook de

activatie.

en tijdens

aapdepriva

verschillen

steld aan 4

dag slapen

t werd ge

De dieren

de was, do

an gewend

ogelijk stre

ctiviteit.

ertraagd he

e van gedr

hypothes

een disso

viteit, en do

langrijk is

matige activ

erpreteren

g.

MEN

rt op de s

een activa

een afnam

orzaakt kun

5 lieten w

is van d

mate van

Zo wordt

de slaapd

tie method

in slaapde

4 of 6 uur

n werd de

edaan doo

werden wa

oor ze te

d. Door de

ess te indu

erstel van

ragsmatige

se dat ee

ciatie tuss

oor oncont

s om de

viteit te a

in termen

stresssyste

atie van d

me laten zi

nnen zijn d

we zien d

de mate

mentale a

een hoge

deprivatie

de aversief

eprivatie d

slaapdepr

hoeveelhe

or de zog

akker geh

verplaatse

eze metho

uceren. Oo

de cortic

e activiteit

en daadw

sen fysiolo

roleerbaar

fysiologisc

nalyseren

n van stres

emen late

e stresssy

en als gev

door versc

dat stresss

van fysie

activiteit en

ere stresss

periode fy

f is. Versc

duur. In ho

rivatie. Aan

eid slaap m

genaamde

ouden doo

en in de k

ode te ge

ok inducee

costeron

van de

werkelijk

ogische

rheid en

che en

om zo

ss of in

en geen

ystemen

volg van

hillen in

systeem

eke en

n stress

systeem

ysiek of

hillende

oofdstuk

ngezien

met een

‘gentle

or ze te

kooi. De

ebruiken

ert deze

O

effectie

slaapde

microsl

zijn pra

zien na

van de

slapen

nog ee

verhoo

W

activati

45 min

kan he

analyse

en de

tijdens

stresss

geïndu

fysieke

wordt g

slaapde

belang

slaapde

O

stressv

gerelat

dat som

periode

respon

was, de

van str

worden

Onze stud

ef is in

eprivatie w

leeps’ te z

aktisch onv

a het beëin

e slaapdep

om het te

en toename

gd was.

We laten

e van het

uten na be

et gevolg

es toonden

gemeten

als na s

systeem ac

ceerd om

e activiteit w

gezien als

eprivatie k

rijk dat h

eprivatie st

Op basis

vol te zijn

eerd was

mmige die

e. Dit was

s. Omdat

enken we

ress of de

n.

dies tonen

het induc

waren er e

ien maar v

vermijdelijk

ndigen van

privatie no

ekort in te

e in NREM

verder zie

SAM-syste

eëindiging

zijn van h

n een corr

fysiologisc

slaapdepri

ctivatie tijd

de dieren

was niet h

de dieren

kan de str

ier rekeni

tudies wor

van onze

n. Er was

aan de fys

ren geagit

s niet teru

dit vooral

dat dit het

e slaapdep

aan dat d

ceren van

enkel zoge

verder war

k. Tevens

n de slaapd

g zichtbaa

halen. De

M slaap de

en dat acu

eem en de

van de sla

het slaapte

relatie tuss

che en ho

vatie zich

dens slaap

n wakker t

oger dan d

wakker zij

resssystem

ing mee

rden geïnte

resultaten

een mild

sieke activ

teerd reag

ug te zien

tegen het

t gevolg is

privatie pr

deze ‘gent

n een sla

enaamde

en de dier

laten de

deprivatie.

ar en geef

resultaten

lta power z

ute ‘gentle

e HPA-as g

aapdepriva

ekort dat w

sen de ma

ormonale

htbaar. Dit

pdeprivatie

te houden

de activite

n. De gedr

men dus s

gehouden

erpreteerd.

n blijkt ‘ge

de stresss

viteit die we

eerden teg

n in de g

t einde va

van een t

rocedure,

N

tle handlin

aaptekort.

‘Non Rap

ren wakker

resultaten

Dit was to

ft aan dat

n beschrev

zien, wat a

e handling’

geeft en da

atie. De m

werd geïn

te van fys

respons. D

t wijst er

e nodig wa

, te onder

it die onde

ragsmatige

sterk beïn

wordt w

.

entle hand

systeem a

erd geïndu

gen het ei

gemeten fy

an de slaa

toename in

maar dit d

Nederland

g’ slaapde

Tijdens

id Eye Mo

r. Deze NR

een NRE

ot 1,5 uur n

t de dieren

en in hoof

aangeeft d

slaapdep

at deze vol

ilde stress

nduceerd.

ieke activit

Deze corr

op dat e

as om de

rsteunen.

er normale

e activiteit

vloeden e

wanneer de

ling’ slaap

activatie te

uceerd. To

nde van d

ysiologisch

apdeprivatie

n slaapteko

dient verd

dse samen

eprivatie m

de period

ovement (

REM ‘micro

EM slaap r

na het beë

n extra zij

fdstuk 4 la

dat de slaa

privatie ee

lledig herst

ssysteem a

Echter, co

teit van de

relatie was

en deel v

fysieke a

De geïndu

e omstandi

van dieren

en daarom

e resultat

pdeprivatie

e zien die

och bemerk

de slaapde

he en hor

e periode

ort en niet

der onderz

vatting

185

methode

de van

(NREM)

osleeps’

rebound

ëindigen

jn gaan

ten ook

apdiepte

n milde

teld zijn

activatie

orrelatie

e dieren

s zowel

van de

activiteit,

uceerde

gheden

n tijdens

m is het

en van

e weinig

e nauw

kten we

eprivatie

rmonale

te zien

t zozeer

zocht te

Nederl

186

V

slaapde

onderlig

van ver

SLAAP

Slaapd

stresss

op de r

stressre

beëind

hoofdst

activati

reflectie

reward

uur te

blootge

voorko

de situ

slaapte

D

gemete

‘frustra

de fysi

vonden

en het

‘operan

van de

Dus, o

hormon

de dier

landse sam

Verschillen

eprivatie

ggende m

rschillende

PDEPRIVA

eprivatie

systemen a

reactiviteit

espons). I

igen van

tuk 5 aan

e maar, z

e van de f

’ situatie e

herstelle

esteld aan

men dat d

uaties. On

ekort was.

De resulta

en hormo

tive non-re

ieke activi

n we geen

t gedrag t

nt-condition

verschille

ndanks da

nale en fys

ren werden

menvatting

nde brein

op de s

echanisme

e systemen

ATIE EN S

kan niet

activeren (

van de str

In hoofdst

de slaapd

‘frustrative

zoals bes

fysieke act

een reflecti

en na be

n de situ

de dieren in

nze studies

aten laten

onale en

eward stres

teit en he

effect van

tijdens de

ning taak’.

nde situati

at er een

siologische

n blootgest

g

n mechan

stresssyste

en in het b

n wel bedis

TRESSSY

t alleen

(basale str

resssystem

uk 4 hebb

deprivatie

e non-rewa

sproken, is

tiviteit van

e is van d

ëindiging

uatie. Dez

n een gea

s laten zi

zien dat

fysiologis

ss’. Ook h

et gedrag

n slaapdep

situatie w

Ook het h

ies was nie

slaaptekor

e respons,

teld.

nismen z

emen. In

brein niet o

scussieerd

YSTEEM R

rechtreeks

ressrespon

men op be

ben we di

bloot te s

ard stress’.

s deze ac

de dieren

e aversivit

van de

ze herste

agiteerde s

en dat er

acute slaa

che respo

ad voorafg

van de d

rivatie op d

waarbij de

herstel van

et beïnvloe

rt was geï

en op het

ijn betrok

dit proef

onderzocht

.

REACTIVIT

s de fys

ns), maar

paalde nie

it onderzo

stellen aan

. Beide situ

ctivatie vo

n, waar de

teit. De die

slaapdepr

lperiode w

staat zoude

r na deze

apdeprivat

ons tijden

gaande sla

ieren tijde

de fysiolog

e dieren w

n de stress

ed door vo

ïnduceerd,

t gedrag, t

kken bij

fschrift zij

t, maar is

TEIT

siologische

kan ook e

euwe situat

cht door d

n ‘novelty

uaties gev

oor ‘novelt

eze voor de

eren krege

rivatie voo

werd geïn

en worden

e 1,5 uur

ie geen e

ns ‘novelt

aapdepriva

ens beide

gisch en ho

wel beloon

srespons n

orafgaand

had dit g

tijdens de

het effe

jn de m

de betrokk

e en hor

een effect

ties (geact

de dieren

exposure

ven stresss

ty exposu

e ‘frustrativ

n de kans

ordat ze

nduceerd

blootgest

nog stee

ffect heeft

ty exposu

atie geen e

situaties.

ormonale r

nd werden

na het beë

e slaapdep

geen effect

situaties w

ct van

ogelijke

kenheid

rmonale

hebben

tiveerde

na het

e’ en in

systeem

re’ een

ve non-

om 1,5

werden

om te

eld aan

eds een

t op de

ure’ en

effect op

Tevens

respons

n in de

ëindigen

privatie.

t op de

waaraan

E

stressv

verschi

waardo

SLAAP

We wa

geactiv

aandac

aandac

verschi

verschi

aandac

D

prestat

beïnvlo

dit verd

reactio

aangele

wordt g

up. Wa

neus in

verdien

de volg

mogelij

is de

resultat

selectie

en imp

T

CSRTT

Er zijn we

volle situati

illen in s

oor het last

PDEPRIVA

aren niet al

veerde stre

chtsconcen

chtsconcen

illende aa

illen de

chtsconcen

De resulta

tie, impuls

oedt en da

der onderz

n time tas

eerd om t

gepresente

anneer het

n het gaa

nt het een

gehouden

jkheid om

mogelijkhe

ten laten

eve en volg

ulsiviteit va

Twee and

T tonen we

inig studie

ie nadat ze

slaapdepriv

tig is de stu

ATIE EN A

lleen geïnt

essrespon

ntratie. M

ntratie neg

andachtsco

huidige s

ntratie test

aten van h

siviteit en

t ook de s

zocht doo

sk’ (5-CSR

te reagere

eerd in 1 v

dier het lic

atje te dru

voedselbe

aandacht

de aandac

eid om de

zien dat v

gehouden

an de diere

ere studie

el een effe

es waarbij

e zijn gede

vatie duur

udies met

AANDACHT

teresseerd

ns, we wa

Meerdere

gatief beïn

oncentratie

studies in

wat het la

hoofdstuk

motivatie

tressrespo

or de diere

RTT). Voor

n op een

van de 5 g

chtsignaal

kken waa

eloning. De

opgesplit

cht te richt

e aandac

voorafgaan

aandacht,

en waren n

es die slaa

ect van voo

dieren wo

epriveerd v

r, slaapde

elkaar te v

TSCONCE

d in de effe

aren ook

studies to

nvloedt, m

e parame

n slaapde

stig maakt

5 laten a

e tijdens

ons niet is

en te train

r het uitvo

licht stimu

aten die a

ziet en bin

ar het licht

eze test ma

st te onde

ten op een

ht voor la

nde slaap

, als geme

niet beïnvlo

apdeprivat

orafgaande

N

orden bloot

van slaap.

eprivatie m

vergelijken

ENTRATIE

ecten van a

geïnteress

onen aan

aar er zij

eters bes

eprivatie

t om de res

al zien da

de ‘opera

beïnvloed

nen in de

eren van

ulus die w

anwezig z

nnen de ge

tsignaal vo

aakt het m

erzoeken.

n gebeurte

angere du

deprivatie

eten in de 5

oed.

tie hebben

e slaapdep

Nederland

tgesteld aa

De studies

methode

.

E

acute slaa

seerd in h

n dat sla

n maar w

studeerd

methode,

sultaten te

at acute s

ant-conditi

. In hoofds

zogeheten

deze taak

willekeurig

zijn in een

estelde tijd

oor korte

mogelijk om

Selectieve

enis. Volge

uur vast t

niet van

5-CSRTT.

n gecombi

privatie op

dse samen

an een po

s die zijn g

en type

apdeprivatie

het effect

aapdepriva

weinig stud

hebben.

-duur e

vergelijke

laapdepriv

ioning taa

stuk 6 heb

n '5-choice

k wordt he

en voor ko

wand van

d reageert

tijd te zie

m de select

e aandach

ehouden aa

e houden

invloed is

Ook de m

neerd me

p de select

vatting

187

otentieel

gedaan,

situatie

e op de

op de

atie de

dies die

Tevens

n type

n.

vatie de

ak’ niet

bben we

e serial

et ratten

orte tijd

de set-

door de

en was,

tieve en

ht is de

andacht

. Onze

s op de

motivatie

et de 5-

tieve en

Nederl

188

volgeho

5-CSRT

een ve

Tevens

slaapde

Dit is n

design

slaapde

worden

betrokk

aandac

bediscu

tonen a

die be

neurob

stresss

CONCL

De stu

hebben

gedrag

verstor

belang

activati

H

van de

beïnvlo

volgens

hormon

parame

landse sam

ouden aan

TT kunnen

erschil in s

s hebben w

eprivatie o

niet gedaan

komt me

eprivatie m

n en elkaar

Het bestu

ken zoude

chtconcent

ussiëren w

aan dat sla

elangrijk

biologische

systeem ac

LUSIES

dies in dit

n ontwikke

smatige e

rende facto

rijk is, voo

e samen m

Het doel v

e stresssys

oeden. We

s ons mod

nale en fys

eters wan

menvatting

ndacht. Ve

n een oorz

laapdepriv

wij de diere

om te voork

n in ander

et onder a

methode zo

r kunnen a

uderen va

en kunnen

tratie, viel

we in dit

aapdepriva

zijn voor

overlap t

ctivatie en

t proefsch

ld, het mog

en aanda

oren gered

or een cor

met de ged

van onze s

stemen, de

e hebben

del, de stre

siologische

neer het

g

rschillen in

zaak zijn v

vatie metho

en de kans

komen dat

re studies.

andere du

odat de res

aanvullen.

an de on

n zijn bij

buiten d

proefschr

atie en stre

r de aan

ussen de

slaap.

hrift bevest

gelijk maa

achtsconce

duceerd wo

rrecte inte

dragsmatig

tudies was

e aandacht

aangetoon

sssysteme

e respons,

dier daarn

n het aanle

voor het vi

ode en -du

s gegeven

de dieren

Het is be

idelijke tra

sultaten tus

nderliggend

de effecte

de onderzo

ift verschi

esssysteem

ndachtconc

processen

tigen dat

kt om mee

entratie p

orden. Tev

erpretatie v

ge activiteit

s om te be

tsconcentr

nd dat acu

en mild beï

de aanda

na wordt

eren van d

nden van

uur speelt

om voor k

geagiteerd

langrijk da

aining prot

ssen studie

de mecha

en van ac

oeksvraag

llende bet

m activatie

centratie.

n betrokke

het experi

erdere horm

arameters

vens beve

van de res

t te bestud

ekijken of s

ratie en str

ute slaapd

ïnvloedt en

achtsconce

blootgeste

e taak en

verschillen

zeer waa

korte tijd te

d de taak z

at er een g

tocollen e

es beter ve

anismen i

cute slaap

van dit

trokken sy

mechanis

Er is e

en bij aand

imenteel d

monale, fys

te mete

stigen onz

sultaten, o

eren.

slaapdepriv

resssystee

deprivatie,

n dat er ge

entratie en

eld aan ‘n

de prestat

nde effecte

rschijnlijk e

herstellen

zouden uit

gestandaar

n een sta

ergeleken

n het bre

pdeprivatie

proefschr

ystemen.

smen beïnv

een intere

dachtconce

diermodel,

siologische

en terwijl

ze studies

om stresss

vatie, door

em reactivi

indien toe

een effect i

op gedrag

ovelty exp

tie in de

en. Ook

een rol.

n van de

tvoeren.

rdiseerd

andaard

kunnen

ein die

op de

ift. Wel

Studies

vloeden

essante

entratie,

dat wij

e, EEG,

stress

dat het

systeem

r middel

teit zou

egepast

s op de

gmatige

posure’,

‘frustra

kan wo

beëind

hormon

geen n

de stre

slaapde

D

slaapte

onbean

mecha

betrokk

interess

stresss

aandac

O

stress

slaapde

herhaa

herstel

chronis

activee

verwac

gedrag

reactivi

van de

interess

verleng

uitsteke

tive non-re

orden verk

iging van

nale respo

egatieve e

esssystem

eprivatie.

De studies

ekort en

ntwoord. Z

nismen ve

ken zijn b

sant. Deze

systemen

chtsconcen

Ondanks d

reactivite

eprivatie a

aldelijk acut

wordt ook

sche slaap

ert en er ge

chten daaro

smatige r

iteit en aa

e slaapdep

sant zijn o

gen of de a

ende basis

eward stre

klaard door

de slaapd

ns met de

effecten zie

en in bela

s in deze

stresssys

Zo is het

erder te on

bij slaap,

e kunnen m

en hu

ntratie.

dat wij late

eit en

andere eff

te slaapde

k gezien b

deprivatie

een comp

om een di

respons.

andachtsco

privatie wo

om ons die

acute slaap

s voor zulk

ess’, een ‘

r het comp

eprivatie e

mate van

en, onders

angrijke m

thesis gev

steem act

belangrijk

derzoeken

stresssys

meer inzic

n conse

en zien dat

de aand

fecten heb

eprivatie nie

bij chronisc

of herhaal

leet herste

ssociatie t

We verw

oncentratie

rdt blootge

ermodel ve

pdeprivatie

e vervolg s

‘operant-co

plete herst

en de nauw

fysieke ac

steunen on

mate betro

ven meer

tivatie, m

k om ook

n. Met nam

teem activ

cht geven i

equenties

t er geen e

dachtsconc

bben. Het

et voldoen

che slaapd

ldelijke acu

el is na be

te zien tus

wachten oo

e aangetas

esteld aan

erder te ge

e dagelijks

studies.

N

onditioning

tel van de

we correla

ctiviteit van

nze resulta

okken zijn

inzicht in

maar er

de achte

me de over

vatie en

in de relat

op stre

effect is va

centratie

is goed

de kunnen

deprivatie s

ute slaapde

eëindiging v

sen de str

ok dat h

st is wanne

n bepaalde

bruiken en

te herhale

Nederland

g taak’ of

stresssys

atie van de

de dieren

ten wel on

bij de co

de comple

blijven no

erliggende

rlappende

aandachts

ie tussen

ess reac

an acute s

kan her

mogelijk d

n herstellen

studies. W

eprivatie d

van de sla

resssystee

hierdoor d

eer het die

e situaties.

n de slaap

en. Ons die

dse samen

de 5-CSR

steem activ

e fysiologis

. Ondanks

nze hypoth

onsequenti

exe relatie

og veel

neurobiolo

mechanism

sconcentra

slaaptekor

ctiviteit e

slaapdepriv

rhaaldelijk

dat de die

n. Een inco

We verwach

de stresssy

aapdepriva

em activatie

de stresss

er na beë

Het zou

deprivatie

ermodel bi

vatting

189

RTT. Dit

vatie na

sche en

s dat we

ese dat

ies van

tussen

vragen

ogische

men die

atie zijn

rt en de

en de

vatie op

korte

eren na

ompleet

hten dat

ystemen

atie. We

e en de

systeem

indiging

daarom

duur te

edt een

Het hee

kunnen

wil hier

Als eer

dankba

heb vee

mij wis

manusc

hoop d

Pim D

bedank

mijn pr

kennis

nieuws

kennis

toepas

Daarna

mijn p

denkwi

Tevens

Gertjan

proefsc

Verder

vivo en

Graag

bedank

jullie ha

bij ond

eft even g

n volbreng

r de gelege

rste gaat m

aar voor de

el van u ge

st over te

cripten en

at u verde

rinkenburg

ken. Ik wil j

romotieond

te maken

ste en mee

opgedaan

. Dank je w

aast wil ik

romotieon

jze. Daarn

s wil ik de

n van Dijk e

chrift.

gaat er ee

n in vitro af

wil ik de

ken: Ann T

ad ik dit pro

der andere

eduurd, m

en zonder

enheid nem

mijn woord

e mogelijkh

eleerd en i

brengen. D

uw geduld

r kan genie

g, als mijn

jou, en Jan

derzoek bij

n met de

est geava

n en vaard

wel voor je

Peter Mee

derzoek.

naast beda

e hooglera

en Andries

en groot da

fdelingen b

mensen d

T., Ann van

oject nooit

e de oper

Dan

maar mijn p

r al die me

men om de

van dank

heden die

k waardee

Daarnaast

d met mijn

eten van u

n coprom

nssen Pha

j jullie uit

farmaceut

nceerde te

digheden k

supervisie

erlo, mijn c

Ik heb ve

ankt voor je

aren van

s Kalsbeek

ankjewel n

bij Janssen

die onder

n H., Annic

t kunnen re

raties en

nkwo

proefschrift

ensen die

eze mense

uit naar Ja

ik heb gek

er uw entho

t wil ik u b

niet al te s

uw welverd

otor wil ik

armaceutic

te voeren

tische ind

echnieken

kunnen ont

e, kritische

copromoto

eel geleer

e feedback

de beoord

k, bedanke

naar iedere

n Pharmace

Pims vera

ck, Christ,

ealiseren. I

de analys

oord

is eindelij

mij hebbe

n te bedan

aap Koolha

kregen om

ousiasme e

bedanken

snelle afro

iende pens

k jou ook

ca, bedank

. Het heef

ustrie en

en een g

twikkelen,

blik, ideeë

or, bedank

rd van je

k op mijn m

delingscom

en voor het

een van de

eutica.

antwoordeli

Gerd, Heid

Ik wil jullie

ses. Ik he

k af! Ik ha

en geholpe

nken

aas, mijn p

aan dit pro

en positivit

voor alle f

nding van

sioen.

k als één

en voor de

ft mij de k

te mogen

geweldig te

die ik van

ën en gedu

en voor zi

e kennis,

manuscripte

mmissie, D

t kritisch d

e Neurosci

ijkheid we

di, Leen e

bedanken

eb veel va

Dank

ad dit proje

en of geste

promotor. I

oject te we

teit, die u g

feedback

dit proefsc

van de

e mogelijkh

kans gegev

n werken

eam. Ik he

daag de d

uld.

ijn inbreng

kritische

en

Domien Be

oorlezen v

ence Rese

rk(t)en als

n Sofie V.

n voor al ju

an jullie g

kwoord

191

ect nooit

eund. Ik

k ben u

erken. Ik

goed op

op mijn

chrift. Ik

eersten

heid om

ven om

met de

eb veel

dag nog

g tijdens

blik en

eersma,

van mijn

earch in

s eerste

Zonder

llie hulp

geleerd.

Dankw

192

Daarna

Zonder

ben blij

heel s

samenw

betrokk

onderz

het toc

en ik be

Hansfri

bereid

rest va

werk h

over H

vind he

en Bart

Dan wi

geholpe

om ee

promot

onder j

Dank je

wil ik b

te blijve

manusc

meede

Graag

het goe

(jamme

DiLab v

dank je

kennis.

woord

aast gaat m

r jullie had

j dat ik dee

erieuze g

werking! L

ken bent

oeken goe

h steeds w

en je nog s

ied, dank

om ieman

n het lunch

eb ik een

ollanders

et leuk dat

t net ouder

l ik de ond

en. Adriaa

en stage

tieonderzo

ouw super

e wel hierv

edanken v

en kijken.

cripten. Da

nken voor

bedank ik

ed verzorg

er dat jij d

voor al jull

e wel voor

.

mijn dank

ik onmog

el heb mog

esprekken

Leen, nog

geweest

ed verlope

weer voor e

steeds dan

je wel voo

d te helpe

h groepje

gezellige

te onthoud

wij contac

rs geworde

derzoekers

an Bouwkn

onderzoe

ek. Ook a

rvisie, je be

voor en tev

voor je enth

Daarnaast

arrel Pemb

mijn 5-CS

alle dierve

en van ‘m

it nooit me

lie hulp, so

r je hulp m

uit naar ju

elijk de die

gen uitmak

n zijn mij

een speci

bij mijn p

n. Ondank

elkaar! Ik h

nkbaar voo

or je hulp

en. Daarna

Leen, Lies

tijd met ju

den, maar

ct zijn blijv

en van Yen

s bedanken

necht, med

k bij Jan

al deed ik

ent altijd je

vens voor j

housiasme

t bedankt v

berton, bed

SRTT studie

erzorgers,

ijn’ diertjes

eer zal lez

oms erg a

met de stat

ullie hulp b

eren 4 of 6

ken van jul

altijd bij

aal dankje

promotieon

ks zoveel p

heb veel pr

or je inzet.

met onde

ast bedan

sbeth, Sara

ullie gehad

ik vrees d

ven houden

nthe, profic

n die mij d

de dankzij

nssen te

mijn stag

e interesse

je advieze

e en ideeë

voor het d

dankt voor

e.

en in het b

s. Ook dan

zen), de m

d-hoc, me

istische an

bij het wak

6 uur lang

lie team. O

gebleven

ewel voor j

nderzoek.

problemen

raktische v

er andere

kt voor je

ah en Sofie

. Ik heb g

dat het me

n en op de

ciat!

door het de

jou heb ik

doen, wa

e en prom

e blijven to

en en kritis

n. Je hebt

oorlezen v

het delen

bijzonder L

nk je wel vo

mensen va

et de appa

nalyse en

kker houde

kunnen w

Onze geze

. Bedankt

jou aange

Mede da

n met de s

vaardighed

de 5-CSR

gezellighe

e E. Zowel

eprobeerd

e niet is ge

e dag dat i

elen van hu

k de moge

at heeft u

motieprojec

nen en bet

che blik. A

mij geleer

van een gr

van je ken

Luc, voor j

oor Donald

n Peira en

ratuur en

met name

en van de

wakker hou

ellige en so

t voor jull

ezien jij he

nkzij jou

et-ups kre

den van je

RTT. Jij be

id, samen

l op als bu

d om alle m

elukt. Lies

ik dit schrij

un kennis

elijkheid ge

uitgemond

ct uiteinde

trokken ge

Abdel Ahna

rd om altijd

root deel v

nnis en het

ullie flexib

d, Frederik

n de mens

software.

e het delen

dieren.

uden. Ik

oms ook

lie fijne

t langst

zijn de

egen we

geleerd

ent altijd

met de

iten het

moppen

beth, ik

jf zijn jij

hebben

ekregen

in dit

elijk niet

ebleven.

aou, jou

d verder

van mijn

kritisch

iliteit en

k, Johan

sen van

Helena,

n van je

Buiten

Jansse

mijn tijd

Door d

eens b

Er gaat

in Gron

beantw

was. S

frustrat

Daarna

gelever

en enth

Graag

alle hul

Mijn tijd

paar ja

tijd sam

Suus.

En dan

Alie, he

op ons

promot

gespre

te steu

woont

ontspa

mij af te

Marian

nog ve

de mense

en die op

d in België

e afstand

ij Janssen

t ook een

ningen voo

woorden va

Sietse de B

tive non-re

aast wil ik

rd aan hoo

housiasme

bedank ik

lp met de S

d in België

aar heb ve

men met

n wil ik graa

et is fijn om

s staan te

tie, af te ro

kken en je

unen en je

en we elka

nning door

e kunnen s

, jullie jare

le jaren va

en die ik

een bepaa

ë, door mij

en drukte

langs te k

woord van

or hun bijd

an mijn vra

Boer, beda

ward onde

k Rolinka

ofdstuk 6,

e. Ik vond h

ook Gera

Skinner Bo

ë begon me

rtoefd. Ik d

mijn Holla

ag mijn vrie

m samen in

wachten

onden. Nog

e bezoekje

e belangste

aar weer v

r vele saun

spreken en

enlange vr

an vriendsc

zojuist he

alde manie

actief te h

heb ik nie

omen. Ma

n dank uit

drage aan

agen of de

ankt voor

erzoek.

Schippers

als onder

het een lee

ard van Oij

ox apparatu

et het won

denk met e

andse huis

endinnen b

n een perio

en daarbi

g even, en

es aan mij

elling te to

vaker zien.

na bezoekj

n je bent a

riendschap

chap bij ko

b genoem

er hebben

helpen of g

et meer de

ar ik ben ju

naar de m

mijn prom

gezellige g

het delen

s bedanke

deel van j

erzame en

jen van de

uur en soft

nen aan de

een grote

sgenootjes

bedanken.

ode te zitte

ij nog ‘eve

we zijn er

in België.

onen. Ik v

. Marian, b

jes en eten

altijd interes

p betekent

men.

md zijn er

bijgedrag

gewoon ee

e kans geh

ullie zeker

mensen van

motieonderz

gesprekke

n van je ke

en. Jij heb

e Masters

ook gezell

e Radboud

tware.

e Patersstr

glimlach t

Maartje,

en met spa

en’ een st

van af. Ik

Hieke, ond

ind het fijn

bedankt vo

ntjes. Jij re

sse blijven

heel veel

nog veel

gen aan m

en gezellig

had om na

niet verge

n de vakgr

zoek. Dan

n als ik ev

ennis voo

bt een be

stage. Beda

lige period

d Universite

raat in Turn

erug aan m

Marieke,

nnende en

tudie, of in

wil je beda

danks de a

n dat je w

oor de gez

eed overal

n tonen. Lie

voor me e

Dank

meer men

mijn onderz

g ‘klapke’ t

a mijn vert

ten!

roep dierfy

nk je wel v

ven op de a

r mijn nov

langrijke b

ankt voor

e.

eit Nijmege

nhout waa

mijn Pater

Mignon, S

n leuke din

n mijn gev

anken voor

afstand wis

weer in Ne

ellige aflei

wel heen

eve Alie, H

en ik hoop

kwoord

193

nsen bij

zoek en

e doen.

rek nog

siologie

voor het

afdeling

velty en

bijdrage

je inzet

en voor

r ik een

rsstraat-

Sara en

ngen die

val een

r je fijne

st jij me

ederland

ding en

om met

Hieke en

p dat er

Dankw

194

Een sp

Tosca.

biologie

beetje

doorge

gezellig

mij elk

makkel

tijdens

wil ik b

gewees

steun,

trots op

ben su

vriends

Daarna

belangs

hier ve

mijn vo

Dan w

steun e

in mijn

mee he

jullie he

Lieve S

je wel v

ook vo

dank u

en vord

eens e

heb ge

woord

peciaal woo

Alweer bi

e. Ik kijk t

de hele o

ebracht en

gheid, pos

ke keer we

lijk (gehad

de opleidin

bedanken

st dat jij o

belangstel

p wat jij al

uper trots

schap nog

aast wil ik

stelling in

el aan geh

oortgang.

il ik natuu

en vertrouw

keuzes. B

ebben geh

eel dankba

Stéfanie, b

voor de le

or een stu

it naar mij

deringen. I

en weeken

noemd, da

ord van da

ijna 13(!) j

terug op e

opleiding

een hech

itiviteit, fijn

eer te mo

d) en ik be

ng een and

voor je ge

ook begon

ling en adv

llemaal, sa

dat jullie

lang zal bl

k vrienden

mijn onde

had. Ook w

rlijk mijn o

wen had ik

Bedankt da

holpen. Oo

aar voor d

edankt voo

uke uitstap

udie in Belg

n schoonfa

k wil jullie

ndje aan m

ank jullie w

ank gaat ui

jaar geled

een leuke

dezelfde v

te vriendsc

ne gesprek

otiveren om

en trots op

dere richtin

ezelligheid

aan een

viezen. Oo

amen met

e straks n

lijven besta

die ik nie

rzoek en v

wil ik mijn h

ouders nog

k dit nooit

at jullie altij

ok bedank

de mogelijk

or het door

pjes die we

gië terecht

amilie. Ik w

tevens be

mijn proefs

wel voor jull

t naar mijn

en begonn

studenten

vakken ge

chap opge

kken en je

m door te

p wat je h

ng, we zijn

d en fijne g

promotieo

ok jij hebt e

Steven, h

naast mij

aan.

et bij naa

voor het b

huidige co

g bedanke

kunnen do

jd voor mij

kt voor julli

kheden en

rlezen van

e hebben

t zou kome

waardeer j

danken vo

chrift moes

lie belangs

n vriendinn

nen wij teg

ntijd same

evolgd en

ebouwd. Ik

e bezoekje

e gaan. Je

hebt bereik

n elkaar alt

gesprekke

onderzoek.

een moeilij

ebt bereik

zullen sta

m heb ge

ieden van

ollega’s bed

en. Lieve

oen. Jullie

j klaar staa

ie vele be

n hulp die

n mijn Nede

gemaakt. W

en. Daarna

ullie belan

oor het opv

st werken.

stelling.

nen en par

gelijkertijd

en. Lillian,

daardoor

k wil je bed

s aan mij

e hebt he

kt. Tosca,

ijd veel blij

en. Het is

. Ik heb ve

ke tijd geh

kt. Lieve Li

aan en ik

enoemd be

de nodige

danken vo

Jos en Ro

hebben m

an en mij o

zoekjes aa

jullie mij

erlandse s

Wie had n

aast gaat e

ngstelling in

vangen van

Familie d

ranimfen L

aan de o

we hebbe

r veel tijd

danken vo

in België.

et niet altij

ook al ko

jven zien. O

voor mij h

eel gehad

had en ik b

illian en To

k hoop da

edanken v

e afleiding

or de inter

oely, zond

mij altijd vrij

overal waa

an België.

hebben ge

stukken. Oo

nou gedach

er een wo

n mijn proe

n Joey als

ie ik niet b

illian en

pleiding

en zo’n

samen

oor al je

Jij wist

jd even

zen we

Ook jou

heel fijn

aan je

ben heel

osca, ik

at onze

voor de

. Ik heb

resse in

er jullie

jgelaten

ar nodig

Ik ben

eboden.

ok dank

ht dat jij

ord van

efschrift

ik weer

bij naam

En dan

wil je b

proef h

proefsc

moest o

ik je no

kijk uit

n als laatst

bedanken

heb gesteld

chrift moes

om te werk

og steeds h

naar onze

te ben ik e

voor je lie

d. Toch bl

st werken

ken. Speci

heel erg da

toekomst

een groot d

fde, steun

leef jij ach

of om 5 u

aal voor m

ankbaar vo

samen wa

dankjewel v

n en geduld

hter mij sta

uur ’s nac

mij ben jij de

oor. En nu

aarin mooie

Wieteke

verschuldi

d. Ik weet

aan, ook w

chts of in h

estijds naa

is het dan

e gebeurte

gd aan Jo

dat ik je

wanneer ik

het weeke

ar België ve

n eindelijk

enissen gep

Dank

ey. Lieve J

geduld erg

k alweer a

end naar J

erhuisd. D

helemaal k

pland staa

kwoord

195

Joey, ik

g op de

an mijn

Janssen

aar ben

klaar! Ik

an.

Wietek

Nether

gradua

Neuros

Groning

Depart

where

caused

Neuroe

project

possibl

Belgium

Drinken

Resear

Pharma

challen

OH-DP

PhD pr

same d

W.H.I.M

Physio

Prof. D

period

Associa

ke Beerling

lands. She

ated in the

sciences s

gen in the

ment of B

she studie

d by metho

endocrinolo

was to stu

e treatme

m for seve

nburg and

rch of J

aceutica N

nges in par

PAT on neu

roject after

departmen

M. Drinke

logy at the

Dr. J.M. Ko

has led to

ate at PPD

C

g was bo

e attended

year 200

specializati

e Netherla

Behavioura

ed the be

otrexate. T

ogy and w

udy the inv

ent with th

en months

d Prof. D

Janssen

N.V., Beers

radigms fo

uroendocri

r Wieteke g

nt of Jans

enburg, in

e University

oolhaas a

o the pres

D in Benne

Curric

rn on Jan

the Athen

1. After th

on and w

ands. Her

al Physiolo

ehavioural

The secon

was superv

volvement

he MCH a

where she

r. J.M. K

Research

se, Belgium

or psychiatr

ine, physio

graduated

sen Resea

n collabor

y of Gronin

nd Dr. P.

sent thesis

kom in the

culum

nuary 15

aeum at th

hat she stu

with the Re

r first rese

ogy under

and neuro

d project

vised by P

of the MC

ntagonist.

e worked u

Koolhaas a

& Deve

m. In this re

ric drug dis

ological an

in 2007. T

arch & De

ration with

ngen in the

Meerlo.

s. Since 2

e Netherlan

m Vita

in the ye

he Drachts

udied Biolo

esearch v

earch proj

r the supe

obiological

was perfo

rof. Dr. G

H and MS

For the t

under the

at the De

elopment,

esearch pro

scovery an

nd behavio

The PhD p

evelopmen

h the De

e Netherlan

The work

011 she w

nds.

C

ae

ear 1983

ter Lyceum

ogy, with t

ariant, at

ect was p

ervision of

l indicators

rmed at th

. van Dijk.

H system

third proje

supervisio

epartment

a divisi

oject, she

nd the effe

ural variab

project was

nt under s

epartment

nds under

she perfo

works as C

Curriculum

in Dracht

m in Drach

he Behavi

the Unive

performed

f Dr. B. B

s of neuro

he Departm

. The aim

in obesity

ect she mo

on of Dr. W

of Neuro

ion of J

studied the

ects of CO2

bles. This

s performed

supervision

of Beha

the superv

ormed dur

Clinical Re

m Vitae

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en, the

ten and

ioural &

ersity of

at the

Buwalda

otoxicity

ment of

m of this

and the

oved to

W.H.I.M.

science

Janssen

e stress

2 and 8-

led to a

d at the

n of Dr.

avioural

vision of

ring this

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List of

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Resear

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ng W, Ko

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2-20.

ng W, Koo

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rch in the N

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aas JM, Dr

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