Adolescent vs. adult-onset nicotine self-administration in male rats: duration of effect and differential nicotinic receptor correlates.
Adolescence is the life stage when tobacco addiction typically begins. Adolescent neurobehavioral development may be altered by nicotine self-administration in a way that persistently potentiates addiction. Previously, we showed that female adolescent rats self-administer more nicotine than do adults and that the increased nicotine intake then persists through the transition to adulthood [E.D. Levin, A. Rezvani, D. Montoya, J. Rose, H. Swartzwelder, Adolescent-onset nicotine self-administration modeled in female rats, Psychopharmacology 169 (2003) 141-149.]. In the current study, male Sprague-Dawley rats were given access to nicotine via the standard operant IV self-administration procedure (nicotine bitartrate dose of 0.03 mg/kg/infusion). One group of male rats started during adolescence the other group started in young adulthood. After the end of the four-week period of self-administration brain regions of the rats were assessed for alpha4beta2 nicotinic receptor binding. We found that male rats, like females, show higher nicotine self-administration when starting during adolescence as compared to starting in adulthood (p<0.001). Indeed, the effect in adolescent males was even greater than that in females, with more than triple the rate of nicotine self-administration vs. the adult-onset group during the first 2 weeks. The adolescent onset nicotine-self-administering rats also had significantly greater high affinity nicotinic receptor binding in the midbrain and the striatum, whereas hippocampal binding did not differ between the age groups. Striatal values significantly correlated with nicotine self-administration during the first 2 weeks in the adult-onset group but not the adolescent-onset rats, suggesting that the differences in self-administration may depend in part on underlying disparities in synaptic responses to nicotine. After the initial 2 weeks, nicotine self-administration in male rats declined toward adult-like levels, as the adolescent rats approached adulthood. This study showed that adolescent male rats self-administer significantly more nicotine than do male adult rats, but that adolescent-onset nicotine self-administration in male rats declines over weeks of continued use to approach adult-onset levels. In a previous study, we found that female rats also show greater nicotine self-administration with adolescent onset vs. adult onset, but that the females continued higher rates of self-administration into adulthood. Our results thus reinforce the concept that the adolescent brain is unusually receptive to the effects of nicotine in a manner that reinforces the potential for addiction.
Levin
Edward D
ED
Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, USA; Department of Pharmacology and Cancer Biology, Duke University Medical Center, USA.
Lawrence
Susan Slade
SS
Petro
Ann
A
Horton
Kofi
K
Rezvani
Amir H
AH
Seidler
Frederic J
FJ
Slotkin
Theodore A
TA
D000375:Aging / Q000502:physiology*; D000818:Animals; D001522:Behavior, Animal; D001921:Brain / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009538:Nicotine / Q000008:administration & dosage*; D018722:Nicotinic Agonists / Q000008:administration & dosage*; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D051381:Rats; D011978:Receptors, Nicotinic / Q000378:metabolism*; D012044:Regression Analysis; D012646:Self Administration / Q000379:methods
D018722:Nicotinic Agonists; D011978:Receptors, Nicotinic; C403531:nicotinic receptor alpha4beta2; D009538:Nicotine