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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
mobiliz
glucoco
levels a
human
sleep
increas
subseq
sleep is
mainly
prolong
depres
despite
levels w
Spiege
D
respon
decrea
1980; R
due to
axis ac
arousa
(Jacobson
The HPA
ain stem, t
, 1996; Ulr
tem norad
es noradre
HPA axis
hiasmatic
es in the
corticoid lev
the end of
zing the e
orticoids d
are suppre
s also sho
fragmenta
sed glucoc
quent recov
s not suffic
been sug
ged sleep
sion (Buck
e a rapid d
were prese
el et al., 199
Despite m
se to acut
se in gluc
Rechtscha
the metho
ctivation is
l and cogn
and Sapo
axis rece
he seroton
rich-Lai an
renergic sy
energic act
activity no
nucleus
levels of
vels are th
f the sleep
energy su
uring slee
essed duri
owed eleva
ation (Spa
corticoid le
very sleep
cient, chron
ggested in
disruption
kley and S
ecline in c
ent in the
99). The m
most studi
te sleep d
cocorticoid
affen et al.,
ods used
s highly d
nitive dem
olsky, 199
eives regul
nergic syst
d Herman
ystem toge
tivity, which
ormally dis
of the hy
corticoste
he lowest e
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
levels du
, 1983; Fo
to induce
ependent
and during
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
There is a
red the ph
ation (Mart
s et al., 19
deprivation
nge. The c
been affec
se after sle
Martin et a
siveness
Meerlo an
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
T
a beha
et al., 2
affects
thesis
affects
activati
AIM AN
Sleep d
physica
remain
effects
respon
hypothe
respon
depriva
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
Howev
We ex
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
dy tempera
Dataquest
emperature
ocomotor
strength o
en, vertica
al changes
nimal’s cag
rate values
heart rate
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
ncurrent
between
resence
e (0.5-4
Hz) an
charact
(4.5-8 H
occasio
EEG w
amoun
15-min
Blood
Blood w
samplin
minimiz
min an
rpm. S
were a
immuno
USA) w
Behav
Behavi
5.0 (No
baselin
immed
period
control
behavio
drinking
behavio
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
tly, 12 µl o
for cortico
Mouse/Rat
sitivity of 3.
cored blin
geningen,
t = -25 unt
r the anima
mmediately
the sam
sses were
ooming (in
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
Novelty ex
Eye Mov
EEG with a
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
area between averages +he corticosteovelty exposndition with erneath the g
e: sleep dep
** *
60 100
*
60 100
ControContro
ges in locomduring the 1
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n the dotted+ SEM for therone measusure (n=4), novelty expograph indica
privation ver
*
**
140 180
*
140 180
ol + non-noveol + novelty
motor activity5-min basel
ol period (indt 15 min exd lines) andhe physiologurements. Thsleep deprivosure (n=5) te the dark (sus non-dep
***
****
*
*
220 260
*
**
Time (m
220 260
elty
y (panel A), ine period (i.icated by thexposure to nd the 75-migical measurhese are shvation withoand sleep d
(black); the 3prived contro
*
300 340
*** ** *
min)
300 340
SD + noSD + no
body tempe.e. last 15 me area betwenovelty or nn post-nove
rements andown for the ut novelty e
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380 420
***
380 420
on-noveltyovelty
erature (panein of dark pe
een the dashnon-novelty elty period. as 10-60 mnon-deprive
exposure (n=with novelty grey) and lignovelty ver
#
#
460 500
#
460 500
**
el B) anderiod), theed lines),exposureData are
min meaned control=5), non-exposureht (white)sus non-
540
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*
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ep (
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)
0
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10
15
RE
M s
lee
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3
4
Wa
kefu
lnes
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Figure 3REM sledeprivatirecoverybetween+ SEM adeprivatiand slee(black); deprived
-20 20
-20 20
A
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C
3. Time courseep (panel Cion or non-dey period andn the dotted land are shoion without nep deprivatiothe 30-min
d control *p<0
60 100
60 100
ControContro
se of change) during the eprived cont
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own for the nnovelty exposon with noverise (grey) a0.05, novelty
140 180
140 180
*
*
*
ol + non-noveol + novelty
es in the amo15-min base
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Sle
220 260
Time
220 260
elty
ount of wakeeline period (ndicated by txposure to nst-novelty ped control connon-deprivede (n=5). The hite) period. -novelty, #p<
eep depriva
300 340
(min)
0 300 34
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efulness (pan(i.e. last 15 mthe area betwovelty or no
eriod. Data arndition witho control condbars undernSignificance
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ation and
0 380 4
40 380 4
*
on-noveltyovelty
nel A), NREMmin of dark pween the daon-novelty (inre expressedut novelty edition with noneath the grae: sleep dep
d novelty ex
420 460
20 460 5
#
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#
# #
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M sleep (panperiod), the 6shed lines), ndicated by d as 15-min axposure (n=ovelty exposaph indicate privation ver
xposure
87
500 540
500 540
#
el B) and6-h sleepthe 1.5-hthe area
averages=7), sleepure (n=6)the dark
rsus non-
Chapte
88
Experi
respon
Sleep d
The am
depriva
respect
asleep.
Sleep
concom
ANOVA
p<0.00
sleep a
p<0.00
p<0.00
(F29,638=
p<0.00
affected
within 1
slightly
sleep s
depriva
Novelty
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
REM slee
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
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009). A
-reward
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, ε=0.5,
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ure and
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Chapte
108
heart ra
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In antic
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seems
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er 5
ate (F4,192=
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otor activity
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te activity
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ody temper
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erone leve
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s. Furtherm
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observed
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d with low
els, plasma
vation + no
.
0 min of th
both non-r
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ward grou
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. During th
levels we
non-rewa
ted for the
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groups.
7, p=0.045
rature (F1,4
ant task, po
ure for the
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erant task,
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er locomot
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he post-op
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mperature
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ese 30 m
roup had a
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5) and a si
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ost-hoc an
e sleep dep
e control +
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ntrol + rewa
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the non-re
ecreased h
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ared to th
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mpared to
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. This was
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ignificant s
0.031).
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ll other gr
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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
±0.04
±0.04
y starting 1.5ter 24 h reconses are shoData are shn ± SEM.
After 24
recovery
63.39±2.2
67.04±2.2
54.75±2.3
57.70±2.8
3.63±0.5
3.10±0.4
10.13±1.0
11.20±1.9
0.82±0.0
0.71±0.0
5 h after overy of own as own for
h
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26
22
31
83
56
41
09
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06
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Figureday, onprocedanimalconditinumbedeprivafor thedepriva
DISCU
The sl
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concom
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reduce
the 5-C
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seve
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e re
spon
ses
(#)
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2
4
6
8
10
12
14
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e 4. Panel A n the experi
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er of perseveation as come control coation versus
SSION
eep-wake
antly prev
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man et al.
d in NRE
ulness dur
s were retu
mitant redu
s. Interesti
their NRE
CSRTT as
Baseline
*
A
shows the nmental day sday) and afessed in thesequent 1.5erative resp
mpared to theondition (n=control *p<0
distributio
vented rats
nt. Only so
val. These
n and ind
, 1979). U
EM sleep
ration. Thi
urned to th
uction in w
ingly, the c
EM duratio
compared
Exp. day
number of pestarting 1.5 fter 24 h ree 5-CSRTT a-h post-depronses for th
e baseline da=8) and sle0.05
ons confirm
s from sle
ome NREM
so-called
dicate an
Upon term
duration
irty minute
heir home
wakefulnes
control ani
n and alm
d to before
CoSl
y 24 h recov
erseverative h after termicovery of slafter 6 h slerivation recohe experimeay. Data are eep deprivat
m that 6
eep. During
M sleep wa
micro slee
increased
mination of
was visib
es upon
cages, an
ss duratio
imals seem
ost do not
e 5-CSRTT
ontrol (n=8)eep depriva
very
delta
per
seve
rativ
e re
spon
ses
-
-
-
Sleep dep
responses iination of sleleep depriva
eep deprivatiovery. Panel ntal day andexpressed ation conditio
h gentle
g sleep de
as present
eps are pra
d sleep p
f the sleep
ble with a
terminatio
other incre
n was vis
m to increa
enter REM
T. The slee
)ation (n=10
-6
-4
-2
0
2
4
6
8
Ex
B
privation a
n the 5-CSReep deprivatation. At theion or the nB shows th
d after 24 has mean +/- Son (n=10).
handling
eprivation,
with a dur
actically un
ressure d
p deprivat
a concomi
n of the
ease in NR
sible for th
ase their ti
M sleep up
ep-deprive
0)
xp. day
*
and the 5-
RTT on the bion or non-d
e experimenton-deprived
he mean chah recovery oSEM and areSignificance
sleep dep
REM sle
ation below
navoidable
during dep
tion proce
tant reduc
5-CSRTT
REM durat
he sleep-d
ime spent
pon termin
ed animals
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
Upon te
to be
hypothe
1982; B
loss, i.e
short-te
D
perform
percen
the 5-C
latencie
motivat
impulsi
indicati
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).
Borbely an
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
Sleep
conseq
occurre
stress
system
a conse
point th
physica
mainly
induced
were a
T
proced
large e
both ch
reductio
proced
that to
challen
power
of slee
mechanism
ation. The
e noradren
system ac
ulness, aro
ore, in ord
xtent these
te sleep de
EQUENCE
deprivatio
quences of
ence of the
system ac
m activation
equence o
hat should
al and men
the same
d by sleep
ble to inve
The results
ure compl
extend. On
hapters a
on in wak
ure. This r
ook place
nge. After t
during NR
ep depriva
ms are in
CRH neu
nergic cell
ctivation ca
ousal, phy
er to interp
e factors m
eprivation i
E OF SLEE
n is often
f sleep de
e stress re
ctivation a
n in respon
of the stres
be evalua
ntal activity
e brain m
deprivatio
stigate the
s of chapte
etely supp
nly short a
rebound i
kefulness
rebound w
before th
termination
REM sleep
tion until
nvolved in
rons in th
clusters in
aused by th
sical activ
pret the re
may have
in our expe
EP LOSS O
n interpret
eprivation
esponse. H
s well. A
nse to slee
ssfulness o
ted is to w
y induced t
mechanisms
on. While it
eir contribu
er 4 and 6
pressed RE
and scatte
in NREM
duration u
was still vis
he animals
n of the sle
was obser
after expo
stress s
e paraven
n the brain
hese pathw
vity, menta
esults corre
contribute
eriments.
OR SLEEP
ted as a
but this in
However, o
common p
p deprivati
of the used
what extent
to keep the
s, may co
t is imposs
tion in our
show that
EM sleep a
red NREM
sleep dur
upon term
sible after
s were ex
eep depriva
rved, that w
osure to n
system ac
ntricular nu
stem are
ways is as
al activity
ectly, it sho
d to stress
P DEPRIVA
stressor t
nterpretatio
other facto
point of di
ion is the r
sleep dep
t the stress
e animals a
ontribute t
sible to fully
experimen
t our gentle
and also d
M microsle
ation was
mination of
1.5 h of re
xposed to
ation proce
was prese
ovelty. Th
Ge
ctivation in
ucleus of t
thought to
sociated w
and stress
ould be fur
s system a
ATION ME
that media
on is main
ors may ha
iscussion
result of sle
privation pr
s system a
awake. All
o stress s
y separate
nts in more
e handling
iminished
eps were
visible wi
the 6-h
ecovery of
the stres
edure also
nt during t
he NREM
eneral Dis
nduced by
the hypoth
o play a ma
with the am
sfulness in
rther discu
activation i
ETHOD
ates the a
nly based
ave contrib
is whether
eep loss pe
rocedure. A
activation is
these fact
system ac
these fact
e detail.
sleep dep
NREM sle
still obser
ith a conc
sleep dep
sleep dep
ssful or co
an elevate
the 1.5 h re
sleep EEG
scussion
151
y sleep
halamus
ain role.
mount of
nduced.
ussed to
induced
adverse
on the
buted to
r stress
er se or
Another
s due to
tors, via
ctivation
tors, we
privation
eep to a
rved. In
comitant
privation
privation
ognitive
ed delta
ecovery
G delta
Chapte
152
power
1979;
observe
depriva
explana
confirm
a sleep
sleep a
was ind
stress s
also be
method
T
we app
experim
conside
(Grass
Hagew
proced
Habitua
caused
1993).
not by
induced
became
publish
aggres
1979; G
agitatio
se. Inte
depriva
therefo
tiredne
er 7
is conside
Borbely, 1
ed in the
ation meth
ation for th
m that 4 an
p loss, wh
after termi
duced, this
system act
e the con
d.
To minimiz
plied the
ments. Thi
ered a mi
i-Zucconi e
woud et al.
ures that
ation to ha
d by the ge
Moreover,
any rude
d only a m
e agitated
hed studies
siveness h
Gessa et a
on and if th
erestingly,
ation and
ore hypothe
ss, rather
ered a ma
1998). Thi
experimen
od and du
his differen
d 6 h of sl
hich cause
nation of s
s does no
tivation ob
nsequence
ze stress
so called
is method
ild proced
et al., 1993
, 2010). In
were use
andling wil
entle handl
, animals w
or unexpe
mild activat
d towards
s do not m
have been
al., 1995;
his is relate
this agita
was not
esize that
than a c
arker for ho
is increase
nt describ
uration wa
nce is not o
leep depriv
s effects t
sleep depr
t mean tha
served du
of the st
confoundin
gentle ha
has show
dure when
3; Grassi-Z
n this thes
d to keep
l reduce t
ling used t
were kept
ected hand
ion of the
the end o
mention ag
n previousl
Tartar et
ed to the s
ation was
reflected
the agitati
onsequenc
omeostatic
ed delta p
ed in cha
as used as
obvious. D
vation by g
that are st
rivation. E
at sleep lo
ring sleep
tressfulnes
ng effects
andling sle
wn to sign
previous
Zucconi et
sis, rats w
p the anim
he extent
to keep the
awake by
dling. Altho
stress sys
of the slee
gitation spe
y reported
al., 2008).
sleep depr
only obse
in a chan
on is the r
ce of stre
c sleep dr
power dur
pter 6 eve
s in the ex
Despite this
gentle hand
till detecta
ven thoug
oss per se
deprivatio
ss induced
of the sle
eep depriv
nificantly r
habituatio
al., 2006;
were habitu
mals awake
of HPA ax
e animals
stroking o
ough our s
stems, it wa
ep depriva
ecifically, h
d after slee
. It remain
rivation pro
erved duri
nge in stre
result of ac
ss induce
rive (Borbe
ring NREM
en though
xperiment
s difference
dling are e
able after
h a signifi
e is respon
n in our ex
d by the
eep depriv
vation proc
reduce sle
on to han
Van der B
uated to th
e during s
xis and ad
awake (Do
or lifting th
sleep depr
as noted th
ation sessi
hyperactiv
ep depriva
s unclear
ocedure or
ng the las
ess system
ccumulatin
d by the
ely and Ne
M sleep w
h the same
in chapte
e, both stu
efficiently in
1.5 h of re
icant sleep
nsible for t
xperiments
sleep dep
ation proc
cedure in
eep times
ndling is in
orght et al
he same h
sleep depr
drenalin ac
obrakovov
em up brie
rivation pro
hat some a
ion. Even
ity and inc
ation (Hicks
what caus
r to sleep l
st stage o
m activatio
ng sleep d
sleep dep
euhaus,
was not
e sleep
er 4. An
udies do
nducing
ecovery
p deficit
the mild
s. It may
privation
cedures,
all our
and is
ncluded
., 2006;
handling
rivation.
ctivation
a et al.,
efly and
ocedure
animals
though
creased
s et al.,
ses this
oss per
of sleep
on. We
ebt and
privation
proced
homeo
neuron
results
accumu
(Tonon
affect
stresso
and wh
relaxed
activati
were re
induced
concep
depriva
behavio
conside
are not
of awak
T
be the
Correla
sleep d
respon
exceed
preced
method
depriva
that wa
stress
involve
sleep d
ure but f
stasis may
al activity
in synapti
ulative effe
ni and Cire
mood. We
or when st
hen the act
d wakefuln
on was ind
eached. W
d to keep
pt of stres
ation can b
our. There
ered minim
t per defin
kening.
The mild s
result of p
ational ana
deprivation
ses. The
d levels re
ing sleep
d. Therefor
ation was n
as induced
system ac
e a mental
deprivation
future stu
y account
is present
ic strength
ect and sl
elli, 2006).
e also hyp
tress syste
tivity of the
ness. Our
duced and
We also sho
the anima
ss, this w
be more a
efore, slee
mally stres
ition stress
stress syste
physical ac
alysis show
n was rela
physical a
ached dur
deprivation
re, a cons
necessary
d to keep t
ctivation. O
challenge
procedure
dies are
for this c
that will in
hening (Ton
eep norma
Disturban
pothesized
em activat
e stress sy
studies s
d that level
owed a clo
als awake a
would imply
appropriate
ep depriv
ssful. This
sed or exp
em activat
ctivity that
wed that t
ated with t
activity lev
ring the la
n. Physica
iderable p
to support
the animal
Our gentle
e therefore
e can be co
needed t
hange in m
nduce syna
noni and C
ally serves
ces in sle
d that slee
tion dissoc
ystems rea
show that
s below th
ose relation
and the st
y that the
ely interpre
vation, as
is importa
periencing
tion observ
the anima
the locom
the pattern
vels reach
ast 30 - 60
al activity w
art of the
t the increa
s awake. A
e handling
mental ac
onsidered
to confirm
mood. Dur
aptic poten
Cirelli, 200
s to down
ep-related
ep depriva
ciates from
ches levels
mild and
hose seen
nship betw
ress syste
e stress s
eted in ter
used in
ant as peo
stressful s
ved during
als displaye
otor activi
ns of the p
hed during
0 min of th
was induce
stress sys
ased physi
Also menta
sleep dep
ctivity indu
minimal.
Ge
m this. Di
ring sleep
ntation. Sy
6). This is
scale the
synaptic
ation can
m the beha
s beyond t
d tempora
during rela
ween the be
em activatio
system ac
ms of met
our expe
ople that s
situations
sleep dep
ed during s
ty pattern
physiologic
g sleep de
he dark pe
ed by our
stem activa
cal activity
al activity
privation p
uced by ou
eneral Dis
isturbed s
deprivatio
naptic pote
s thought to
synaptic s
homeostas
be consid
avioural re
those seen
ry stress
axed wake
ehavioural
on. In view
ctivation by
tabolic sup
eriments, c
tay awake
during this
privation m
sleep depr
during an
cal and ho
eprivation
eriod imme
sleep dep
ation durin
y and wake
may contr
procedure
ur gentle h
scussion
153
synaptic
on, high
entation
o be an
strength
sis may
dered a
esponse
n during
system
efulness
activity
w of our
y sleep
pport of
can be
e longer
s period
may also
rivation.
nd after
ormonal
did not
ediately
privation
g sleep
efulness
ribute to
did not
handling
Chapte
154
W
system
contrib
the sle
can be
that ma
and wa
activati
We the
depriva
induced
activitie
psycho
and ne
should
studies
will res
SLEEP
Even t
system
affect s
control
facing n
The pr
neuroe
expose
depriva
and tra
exposu
the com
er 7
While it is
m activation
ution in ou
ep depriva
considere
ay account
akefulness
on as wel
erefore con
ation proce
d normal
es done t
ological or
euroendoc
be taking
s. Also, diff
ult in differ
P DEPRIVA
though sle
ms, this doe
stress syst
led stimulu
new challe
resent stu
endocrine s
ed to novel
ation. Both
anslational
ure should
mmonly us
s impossib
n in respo
ur experim
ation proce
ed minimal
t for the st
induced to
l. Normal a
nclude tha
edure, we
physical
o prevent
physical a
crine syste
g into acc
ferences in
rences in s
ATION AN
eep depriv
es not exc
tem reacti
us-poor co
enges or st
dy aimed
stress syste
lty and in c
situations
value. As
be interpre
sed stress
le to com
onse to sl
ments in mo
edure was
. We did s
tress syste
o keep the
activity lev
at, in our e
successf
activity. In
t the orga
activity an
ems that s
count whe
n mental an
stress syste
ND STRESS
ation only
clude the p
vity to cha
onditions b
tressors on
to show
ems, affec
chapter 5 t
s were car
s was dis
eted in term
s interpreta
pletely sep
leep depri
ore detail.
minimized
show that a
em activati
e animals a
vels as com
experiment
fully minim
n controlle
anism to f
nd hence i
support th
en interpre
nd physica
em activat
S RESPON
mildly aff
possibility t
allenges. T
but will be
n top of the
whether
cts stress re
to frustrativ
efully chos
scussed, s
ms of meta
ation, wher
parate the
vation, we
We show
d and that
a significan
ion. Howev
awake acc
mpared to
s, by using
mized stres
ed studies
fall asleep
nduce act
his activity
eting outco
al activity in
ion across
NSIVITY
fects the
that acute
This will n
ecome not
e deprived
sleep dep
esponsivity
ve non-rew
sen and ha
tress resp
abolic supp
reas for fr
e possible
e were ab
ed that the
the menta
nt sleep de
ver, the be
counts for t
wakefulne
g the gent
ss and me
s but also
p will alwa
tivation of
y. Therefo
omes of
nduced by
s sleep dep
basal activ
sleep dep
ot be evid
ticeable w
sleep (Me
privation, b
y. In chapt
ward stress
ave good
ponse activ
port of beh
rustrative n
causes of
ble to stud
e stressful
al activity i
eficit was i
ehavioural
the stress
ess were re
tle handlin
ental activ
in real l
ays induce
the physi
ore, these
sleep dep
sleep dep
privation st
vity of the
privation d
dent under
when subje
eerlo et al.
by acting
ter 4 the ra
s after acut
ecological
vation by
aviour rath
non-reward
f stress
dy their
ness of
induced
induced
activity
system
eached.
g sleep
vity and
ife, the
e some
ological
effects
privation
privation
udies.
e stress
oes not
r strictly
ects are
, 2008).
on the
ats were
te sleep
validity
novelty
her than
d stress
the com
novelty
recove
not in
studies
B
respon
measu
temper
depriva
anticipa
Further
were n
affect s
uncont
may n
stresso
2005).
novelty
had be
during
quantif
studies
conclud
challen
activati
S
deprive
used d
sleep d
(Meerlo
Two st
respon
mmonly us
y or frustra
ry period a
an agitate
s show that
Both studie
ses to n
rements o
rature. Als
ation. Acut
ation of th
rmore, the
not affecte
stress sys
rollable an
ot affect
ors (Martin
We tried t
y exposure
een expose
the opera
ication of
s no chang
de that des
nge when
on.
Studies ex
ed are lim
ifferent sle
deprivation
o et al., 20
tudies sho
se to brief
sed stress
ative non-
after sleep
ed state an
t a sleep d
es also sh
novelty ex
of plasma
so, locom
te sleep d
he operant
e recovery
d by prior
stem react
nd unpredic
the activa
n, 1981; M
to assess t
e and duri
ed to sleep
ant task w
psycholog
ges in the
spite a slee
looking a
xposing rod
ited in nu
eep depriva
n methods
002; Suche
owed that
f restraint
interpretat
-reward str
p deprivatio
nymore wh
eficit was s
ow that ac
xposure o
corticoste
motor activ
deprivation
t task or t
of the res
r sleep de
ivity to a
ctable one
ated stress
Martin and
this aspec
ng the fru
p deprivatio
was unaffe
gical perce
behaviour
ep deficit,
at our me
dents to a
mber. Mor
ation durat
s, thereby
ecki et al.,
20 h of s
stress wh
tion seems
ress after
on was ind
hen expos
still presen
cute sleep
or frustra
erone, he
vity levels
n did also
to the rew
sponses a
privation.
controllab
e. Human s
s respons
Chen, 19
ct by monit
ustrative no
on. The pe
ected by p
eption in a
r of the an
rats in our
easuremen
stressful c
reover, the
tions, diffe
making it
2002; Sg
sleep dep
ereas 48
s to be cor
a brief 1
duced to m
sed to the
nt after this
deprivatio
ative non-
eart rate,
s were u
o not affe
warded con
after the c
Altogether
le and pre
studies sug
se but can
84; Martin
toring beha
on-reward
erformance
prior sleep
nimals is
nimals wer
r experime
nts of beh
challenge
e studies
erent types
t hard to
oifo et al.,
rivation di
h of sleep
Ge
rrect. Rats
.5 h recov
make sure
challenge
s recovery
on does no
-reward s
blood pre
unaffected
ect the str
ndition of
hallenges
r, sleep de
edictable s
ggest that
n affect t
n et al., 19
aviour of th
challenge
e, impulsiv
p deprivati
not obviou
re found. W
ents were a
haviour an
after they
that have
s of challen
fully comp
, 2006; No
d not affe
p deprivatio
eneral Dis
s were exp
very perio
the anima
e. Results
period.
ot affect the
stress bas
essure an
by prior
ress respo
the opera
were term
eprivation
situation o
sleep dep
he percep
986; Zoha
he animals
e after the
ity and mo
on. Even
us, in the
We can th
able to dea
nd stress
have been
been don
nges and d
pare their
ovati et al.,
ect the HP
on and 8
scussion
155
osed to
od. This
als were
in both
e stress
sed on
d body
r sleep
onse in
nt task.
minated,
did not
or to an
privation
ption of
r et al.,
s during
animal
otivation
though
present
herefore
al with a
system
n sleep-
ne have
different
results
, 2008).
PA axis
days of
Chapte
156
sleep r
pituitary
respon
depriva
et al., 2
gradua
sensitiv
discuss
the nor
effect o
prolong
there is
2008).
develop
(Meerlo
neuron
stimula
occurre
occurs
as the
also in
showed
chronic
particu
Brown
attenua
(Cape
and on
Hensle
with re
sensitiv
for day
activity
er 7
restriction d
y ACTH r
se remain
ation on str
2006; Nov
al changes
vity (Roma
sed, the C
radrenergic
of acute sl
ged sleep
s little and
It has also
ping altera
o et al., 2
al activity
ation that
ed in the s
in other b
CRH syste
n cognitive
d that the
c sleep res
larly, in the
et al., 20
ating brain
and Jones
ne is medi
er, 2006). S
peated 20
vity of pos
ys, even a
or adrena
did (Meerl
response
ned unalte
ress reactiv
vati et al., 2
in the bra
an et al., 20
RH neuron
c cell clust
leep depriv
deprivatio
controvers
o been sug
ations in
2008). Acu
y. Chronic
can caus
striatum an
rain areas
em is not
e, emotion
serotoner
striction. Th
e brain ste
012). Sero
systems r
s, 1998; B
ating the s
Studies sh
0 h sleep d
tsynaptic s
fter unrest
al stress h
o et al., 2
was signif
red. Thes
vity may a
2008). Chr
ain that ma
005; Roma
ns in the p
ers in the
vation on t
on can cha
sial eviden
ggested tha
CRH sign
ute sleep
c sleep de
se reduced
nd pituitar
is unknow
only involv
al and be
rgic system
he seroton
em’s sleep
otonin is t
responsibl
rown et al
stress resp
howed that
deprivation
serotonin-1
tricted rec
hormones (
002; Nova
ficantly da
e findings
ccumulate
ronic sleep
ay affect s
an et al., 20
paraventric
brain stem
the stress
ange the r
ce for this
at chronic
alling, but
deprivation
eprivation
d CRH se
ry (Fadda
wn but wou
ved in the
ehavioural
m is affect
ergic syste
p generatin
hought to
e for cortic
., 2012). T
ponse and
t chronic s
n per day,
1A recepto
overy slee
(Roman et
ati et al., 2
ampened,
suggest
e over time
p deprivati
stress syst
006; Nova
ular nucleu
m are thoug
systems.
regulation
(Bergman
sleep depr
t only few
n is assoc
may res
ensitivity.
and Fratta
uld be inter
regulation
arousal (
ted by chr
em is invol
ng system
prepare
cal activati
The seroto
d emotiona
sleep restr
can cause
ors. This re
ep, and w
t al., 2005
008). Part
the adren
that the
(Meerlo e
on or restr
tem respo
ti et al., 20
us of the h
ght to play
It has bee
of sympa
nn et al., 19
rivation ca
w studies
ciated with
ult in chr
A study s
a, 1997). W
resting to i
n of the str
(Koob, 199
ronic sleep
ved in slee
(Jouvet, 1
the organ
on and be
nin system
ality (Schw
riction, con
e a gradua
educed se
was not me
5; Roman e
ticularly, w
nal cortico
effects of
et al., 2002
riction may
nsivity and
008). As ha
hypothalam
a main rol
en suggest
athetic acti
989; Meerl
n cause gr
have bee
h increase
ronic CRH
showed th
Whether th
investigate
ress respo
99). Studie
p deprivati
ep regulati
999; Ursin
ism for sl
ehavioural
m has mor
wartz et al.
nsisting of
al reduction
ensitivity pe
ediated by
et al., 200
while the
osterone
f sleep
; Sgoifo
y cause
d stress
as been
mus and
e in the
ted that
vity but
lo et al.,
radually
n done
ed CRH
H over-
hat this
his also
e further
nse but
es also
ion and
on, and
n, 2002;
leep by
arousal
re roles,
., 1999;
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
er controlle
othesis tha
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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
esearch
List of
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Beerlin
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f publicati
ng W, Ko
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ng W, Koo
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rch in the N
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