Adolescent brain and behavior Agerelated sensitivities to natural

Adolescent brain and behavior: Age-related sensitivities to natural rewards and drugs Linda Patia Spear Binghamton University Supported in part by grants R 01 DA 19071, R 37 AA 12525 and R 01 AA 12150

Adolescence Ø transition 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

Social CPP Adult Adolescent Coefficient (%) 60 Control Paired 45 30 15 0 Group Isolate Group Subject Housing Isolate

For adolescents, social history of stimulus animal matters Coefficient (%) 75 group-housed partner isolate-housed partner 60 Control Paired 45 30 15 0 Group Isolated Group Subject Housing Isolated

Social Avoidance during conditioning Adolescent Social Avoidance (s) 120 group-housed partner isolate-housed partner Group 90 60 30 0 Isolate Subject Housing Isolate

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 nondeprived 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 Novelty CPP Coefficient (%) 60 Adolescent Adult 50 40 Control Paired 30 20 10 0 Group Isolate Group Subject Housing Isolate

Novelty CPP –males Time with object during condit. Adolescent Adult 180 60 Coefficient (%) Time with Object (s) 225 135 90 45 Novelty CPP Adolescent Adult 50 40 Control Paired 30 20 10 0 0 Group Isolate Subject Housing Group Isolate Group Subject Housing Isolate

Novelty CPP – females Time with object during condit. Time with Object (s) 225 Adolescent Adult 180 135 90 45 0 Group Isolate Subject Housing

Novelty CPP – females Time with object during condit. Adolescent Adult 180 135 90 45 0 60 Coefficient (%) Time with Object (s) 225 Novelty CPP Adolescent 50 Adult Control Paired 40 30 20 10 0 Group Isolate Group Subject Housing Isolate

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 sine (% Pellets from LDH) % Pellets received from LDH 1. 4 ADOL ADULT 1. 2 1. 0 0. 8 0. 6 0. 4 1 2 3 4 5 6 7 8 Experimental Day 9 10 11 12

(a) Impulsivity defined as SDH pokes during delay on Day 7 (b) Impulsivity defined as % rewarded pokes on Day 8 10 10 LOW IMPUL HI IMPUL 8 6 4 2 0 Ethanol intake (g/kg) Interaction between impulsivity and ethanol intake LOW IMPUL HI IMPUL 8 6 4 2 0 ADOL ADULT Age

Functional consequences of adolescent brain sculpting • Relationship to hormonal reawakening of puberty? • Support continued cognitive/emotional development Ø Modulate highly conserved adolescent behaviors directed towards natural rewards (social stimuli, risk taking/novelty seeking/impulsivity) ØInfluence sensitivity to and motivation for other reinforcing/rewarding stimuli, including drugs

Nicotine-induced CPP (0. 6 mg/kg; biased design; 1 trial/day, saline control; group housed) Coefficient (%) 50 Adolescents Adults 30 Initial Test 10 -30 -50 Saline Nicotine Saline Treatment Nicotine

Locomotor Activity during Conditioning Adolescents Number of Bouts 100 Adults 80 60 40 Saline Nicotine 20 0 1 2 3 4 1 Exposures 2 3 4

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 • 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 • 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 For futher info: lspear@binghamton. edu