Age-dependent effects of low-dose nicotine treatment on cocaine-induced behavioral plasticity in rats.
BACKGROUND
Epidemiological evidence of early adolescent tobacco use, prior to that of marijuana and other illicit drugs, has led to the hypothesis that nicotine is a "gateway" drug that sensitizes reward pathways to the addictive effects of other psychostimulants.


OBJECTIVE
To test this hypothesis, we have compared the effect of a brief, low-dose nicotine pretreatment of adolescent and adult rats on subsequent locomotor response to acute and chronic cocaine.


METHODS
Adolescents, aged postnatal day (P) 28, and adults, aged P86, were given four daily injections of saline or nicotine (0.06 mg/kg, i.v.). At P32 and P90, rats were given acute injections of cocaine (0, 0.4 or 1.0 mg/kg, i.v.) and monitored for locomotor activity in either a habituated or novel test environment. To examine cocaine sensitization, rats were treated for 3 days with saline or cocaine (0.4 mg/kg, i.v.), and, after 1 day of withdrawal, were given a challenge dose of cocaine (0.4 mg/kg, i.v.).


RESULTS
Nicotine pretreatment did not affect acute, drug-induced locomotor activity at either age. However, age differences in cocaine response were observed, with adolescent animals showing enhanced locomotor activity in the novel environment. Adolescent controls did not exhibit cocaine-induced locomotor sensitization, whereas adults did. Nicotine pretreatment during adolescence promoted the development and expression of a sensitized response to repeated cocaine exposure similar to that observed in saline-pretreated adult controls.


CONCLUSIONS
These findings show that brief pretreatment with nicotine, in a low dose comparable to that inhaled in 2-4 cigarettes, enhances cocaine-induced behavioral plasticity in adolescent rats.
McQuown
Susan C
SC
Department of Pharmacology, School of Medicine, University of California, 360 Med Surge II, Irvine, CA 92697, USA. smcquown@uci.edu
Dao
Jasmin M
JM
Belluzzi
James D
JD
Leslie
Frances M
FM
D000222:Adaptation, Physiological / Q000187:drug effects*; D000375:Aging; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D003042:Cocaine / Q000494:pharmacology*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005106:Exploratory Behavior / Q000187:drug effects; D008124:Locomotion / Q000187:drug effects; D008297:Male; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D018765:Dopamine Uptake Inhibitors; D018722:Nicotinic Agonists; D009538:Nicotine; D003042:Cocaine