title: Effects of baclofen on conditioned rewarding and discriminative stimulus effects of nicotine in rats.
abstract: 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.
authors.affiliation: National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services, Baltimore, MD, USA. bernard_lefoll@camh.net
authors.forename: Bernard
authors.initials: B
authors.lastname: Le Foll
authors.forename: Carrie E
authors.initials: CE
authors.lastname: Wertheim
authors.forename: Steven R
authors.initials: SR
authors.lastname: Goldberg
mesh_terms: 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
chemical_list: D018755:GABA Agonists; D018722:Nicotinic Agonists; D009538:Nicotine; D001418:Baclofen