Effects of baclofen on conditioned rewarding and discriminative stimulus effects of nicotine in rats.
Neurochemical studies suggest that baclofen, an agonist at GABA(B) receptors, may be useful for treatment of nicotine dependence. However, its ability to selectively reduce nicotine's abuse-related behavioral effects remains in question. We assessed effects of baclofen doses ranging from 0.1 to 3mg/kg on nicotine-induced conditioned place preferences (CPPs), nicotine discrimination, locomotor activity and food-reinforced behavior in male Sprague-Dawley rats. The high dose of baclofen (3mg/kg) totally eliminated food-reinforced responding and significantly decreased locomotor activity. Lower doses of baclofen did not have nicotine-like discriminative effects in rats trained to discriminate 0.4mg/kg nicotine from saline under a fixed-ratio 10 schedule of food delivery. Lower doses of baclofen also did not reduce discriminative stimulus effects of the training dose of nicotine and did not significantly shift the dose-response curve for nicotine discrimination. Rats treated with the high 3mg/kg dose of baclofen did not express nicotine-induced CPP. These experiments, along with previous reports that baclofen can reduce intravenous nicotine self-administration behavior, confirm the potential utility of baclofen as a tool for smoking cessation.
Le Foll
Bernard
B
National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services, Baltimore, MD, USA. bernard_lefoll@camh.net
Wertheim
Carrie E
CE
Goldberg
Steven R
SR
D000818:Animals; D001418:Baclofen / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D003216:Conditioning, Operant / Q000187:drug effects* / Q000502:physiology; D004192:Discrimination, Psychological / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D018755:GABA Agonists / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012055:Reinforcement Schedule; D012201:Reward
D018755:GABA Agonists; D018722:Nicotinic Agonists; D009538:Nicotine; D001418:Baclofen