Adolescent brain and behavior: Age-related sensitivities to natural rewards and drugs

Linda Patia Spear

Binghamton University

Supported in part by grants R01 DA19071, R37 AA12525 and R01 AA12150

Adolescencetransition between childhood/immaturity and

adulthood/maturity• prototypic age ranges:

humans: 12-18 yrs. (early as 8-10; late as 25)rats: 28-42 days (early as 23-25; late as 55+)

• highly conserved physiological transitions:- puberty- other hormonal changes; growth spurt- neural transformations

• common age-typical behavioral characteristics- increases in peer-directed social behavior - risk taking/novelty seeking/sensation seeking, impulsivity, etc.[species-specific characteristics as well]

Forebrain changes in Adolescents

• Prefrontal Cortex (PFC)– Reduced excit. drive, myelination (humans, primates, rats)

– Decrease in PFC volume (humans & rodents)

– Peak of DA innervation (humans, primates, rats)

– High DA turnover early followed by decline (rats)

– Decline in NMDA-R binding (rats)

• Nucleus Accumbens/ Striatum– Low DA turnover early followed by increase (rats)

– Decline in DA-R binding (esp. striatum) (rats)

• Hippocampus - myelination (humans, rodents)

– Decline in NMDA-R binding (rats)

• Amygdala

– increased/altered patterns of activity (humans, rodents)

– Increase in amygdala-PFC connectivity (rodents)

Functional consequences of adolescent brain sculpting

• Relationship to hormonal reawakening of puberty?• Reduction in brain energy utilization, and support

of continued cognitive/emotional development• Modulate highly conserved adolescent behaviors

directed towards natural rewards

Characteristic adolescent behaviors

• Increases in social interactions/peer affiliations– Develop social

skills/support

– Guide choice behavior

– (may be associated with an increase in parent/ adolescent conflict)

CONDITIONED PLACE PREFERENCE

Group Isolate0

15

30

45

60

ControlPaired

Adolescent

Subject Housing

Coe

ffic

ient

(%

)

Group Isolate

Adult

Social CPP

Group Isolated0

15

30

45

60

75

ControlPaired

group-housed partner

Subject Housing

Coe

ffic

ient

(%

)

Group Isolated

isolate-housedpartner

For adolescents, social history of stimulus animal matters

Group Isolated0

15

30

45

60

75

ControlPaired

group-housed partner

Subject Housing

Coe

ffic

ient

(%

)

Group Isolated

isolate-housedpartner

For adolescents, social history of stimulus animal matters

Subject Housing

Social Avoidance during conditioning

Group Isolate0

30

60

90

120 group-housedpartner

Soc

ial A

void

ance

(s)

Group Isolate

isolate-housedpartner

Adolescent

Social Avoidance during conditioning

Group Isolate0

30

60

90

120 group-housedpartner

Subject Housing

Soc

ial A

void

ance

(s)

Group Isolate

isolate-housedpartner

Adolescent

Social CPP

Adolescent animals are unusually sensitive to social stimuli-Adolescents (but not adults) show social CPP even when socially replete-Socially deprived adolescents exhibit marked increases in social behavior and are socially “ostracized” by non-deprived peers

Characteristic adolescent behaviors

• Increases in social interactions/peer affiliations– Develop social

skills/support

– Guide choice behavior

– (may be associated with an increase in parent/ adolescent conflict)

• Increases in risk-taking, novelty-seeking, sensation-seeking, impulsivity– Impetus for exploring new

territories, aiding in emigration

– Enhance probability of reproductive success (Wilson & Daly)

– Foster peer acceptance (Shedler

& Block)

Novelty CPP –males

Group Isolate0

10

20

30

40

50

60

ControlPaired

Adolescent

Subject Housing

Coe

ffic

ient

(%

)

Group Isolate

Adult

Novelty CPP

0

45

90

135

180

225

Tim

e w

ith O

bjec

t (s

)

Group Isolate

Adolescent

Group Isolate

Adult

Subject Housing

Novelty CPP –males

Time with object during condit.

Group Isolate0

10

20

30

40

50

60

ControlPaired

Adolescent

Subject Housing

Coe

ffic

ient

(%

)

Group Isolate

Adult

Novelty CPP

Group Isolate0

45

90

135

180

225 Adolescent

Subject Housing

Tim

e w

ith O

bjec

t (s

)

Group Isolate

Adult

Novelty CPP – females

Time with object during condit.

Group Isolate0

45

90

135

180

225 Adolescent

Subject Housing

Tim

e w

ith O

bjec

t (s

)

Group Isolate

Adult

Group Isolate0

10

20

30

40

50

60 Adolescent

Subject Housing

Coe

ffic

ient

(%

)

ControlPaired

Group Isolate

Adult

Novelty CPP – females

Time with object during condit. Novelty CPP

Novelty CPP

•Novelty exploration increased during adolescence

•Novelty CPP more robust in adolescent than adult males

•No age difference in novelty CPP in females

•Novelty exploration ≠ novelty reward

Impulsivity in adolescence

Arc

sin

e (%

Pel

lets

fro

m L

DH

)

Experimental Day

1 2 3 4 5 6 7 8 9 10 11 12

0.4

0.6

0.8

1.0

1.2

1.4ADOLADULT

% Pellets received from LDH

Impulsivity defined as SDH pokes during delay on Day 7

Interaction between impulsivity and ethanol intakeE

than

ol in

take

(g/

kg)

Eth

anol

inta

ke (

g/kg

)Age Age

ADOL ADULT

0

2

4

6

8

10

ADOL ADULT

0

2

4

6

8

10

LOW IMPULHI IMPULLOW IMPUL

HI IMPUL

Impulsivity defined as % rewarded pokes on Day 8

(a) (b)

Functional consequences of adolescent brain sculpting

• Relationship to hormonal reawakening of puberty?• Support continued cognitive/emotional

development Modulate highly conserved adolescent

behaviors directed towards natural rewards (social stimuli, risk taking/novelty seeking/impulsivity)

Influence sensitivity to and motivation for other

reinforcing/rewarding stimuli, including drugs

Treatment

InitialTest

Saline Nicotine -50

-30

-10

10

30

50Adolescents

Coe

ffic

ient

(%

)

Saline Nicotine

Adults

Nicotine-induced CPP(0.6 mg/kg; biased design; 1 trial/day, saline control; group housed)

Exposures

43210

20

40

60

80

100

Saline Nicotine

AdolescentsN

umbe

r of

Bou

ts

4321

Adults

Locomotor Activity during Conditioning

Summary• Adolescence as a highly conserved developmental stage with certain common

neurobehavioral features• Sculpting of adolescent brain in mesocorticolimbic regions may influence reward-

related behaviors• Indeed, adolescents generally:

– spend more time engaged with social stimuli and novelty and are more impulsive than adults– find:

• Social stimuli• Novelty

• Nicotine more rewarding/rewarding under more circumstances than adults

• Questions for the future:– Neural substrates underlying specific adolescent-typical behaviors– Adolescent-associated alterations in incentive motivation or hedonic value?

Collaborators• FACULTY collaborators:

– Terry Deak– Juan Molina– Lena Varlinskaya– Brent Vogt– Norman Spear

• Undergrad. honors students:– Bonnie Vastola– Kristin Osiecki – Tom Washburn– Mike Hernandez– Michelle Baretto– Scott Falkowitz

• Former and current graduate trainees: – Marisa Silveri– James Campbell– Nina Katovic– Drew Douglas– Raj Pottayil– Steve Brunell– Tammi Doremus– Rob Ristuccia– Courtney Vetter– Amanda Willey– Carrie Wilmouth

For futher info: lspear@binghamton.edu