Age-dependent effects of nicotine on locomotor activity and conditioned place preference in rats.
BACKGROUND
Most adult smokers start smoking during their adolescence. This adolescent initiation may be due to multiple factors, but little evidence is available regarding whether their brains are differentially sensitive to the addictive effects of nicotine during adolescence.


OBJECTIVE
To test the hypothesis that adolescents are more sensitive than adults to nicotine's rewarding actions.


METHODS
An unbiased, counterbalanced, place-conditioning procedure was used to examine drug-induced reward and locomotor activity. Early adolescent (postnatal day 28), late adolescent (P38) and adult (P90) rats received either saline or nicotine (0.125, 0.25 or 0.5 mg/kg, s.c.) and were tested for place conditioning.


RESULTS
During early adolescence, a single nicotine injection (0.5 mg/kg) induced significant conditioned place preference (CPP). In contrast, during late adolescence or adulthood, nicotine did not induce CPP after either one or four conditioning trials. Initial locomotor responses to acute nicotine administration during the first conditioning trial also differed with age, with no effect at P28, but substantial inhibitory responses at all doses studied (0.125-0.5 mg/kg) at later ages. Although not differing in their initial locomotor response to nicotine, there was a significantly greater tolerance/sensitization during the second and subsequent drug exposures in late adolescents than in adults.


CONCLUSIONS
These findings provide evidence that adolescent brain is differentially sensitive to both the acute and repeated effects of nicotine relative to adult brain. Furthermore, there are significant differences in nicotine sensitivity between early and late phases of adolescence.
Belluzzi
James D
JD
Department of Pharmacology, College of Medicine, University of California, Irvine, CA 92697-4625, USA. belluzzi@uci.edu
Lee
Alex G
AG
Oliff
Heather S
HS
Leslie
Frances M
FM
D000375:Aging / Q000502:physiology*; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003216:Conditioning, Operant / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004361:Drug Tolerance; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013239:Stereotyped Behavior
D018722:Nicotinic Agonists; D009538:Nicotine