title: Varenicline decreases nicotine self-administration and cue-induced reinstatement of nicotine-seeking behaviour in rats when a long pretreatment time is used.
abstract: Effects of varenicline (Champix), a nicotinic partial agonist, were evaluated on subjective effects of nicotine (drug discrimination), motivation for nicotine taking (progressive-ratio schedule of intravenous nicotine self-administration) and reinstatement (cue-induced reinstatement of previously extinguished nicotine-seeking behaviour). Effects on motor performance were assessed in rats trained to discriminate nicotine (0.4 mg/kg) from saline under a fixed-ratio (FR 10) schedule of food delivery and in rats trained to respond for food under a progressive-ratio schedule. At short pretreatment times (5-40 min), varenicline produced full or high levels of partial generalization to nicotine's discriminative-stimulus effects and disrupted responding for food, while there were low levels of partial generalization and no disruption of responding for food at 2- or 4-h pretreatment times. Varenicline (1 and 3 mg/kg, 2-h pretreatment time) enhanced discrimination of low doses of nicotine and to a small extent decreased discrimination of the training dose of nicotine. It also dose-dependently decreased nicotine-taking behaviour, but had no effect on food-taking behaviour under progressive-ratio schedules. Finally, varenicline significantly reduced the ability of a nicotine-associated cue to reinstate extinguished nicotine-seeking behaviour. The ability of varenicline to reduce both nicotine-taking and nicotine-seeking behaviour can contribute to its relatively high efficacy in treating human smokers.
authors.affiliation: Translational Addiction Research Laboratory, Centre for Addiction and Mental Health, Toronto, Canada. bernard_lefoll@camh.net
authors.forename: Bernard
authors.initials: B
authors.lastname: Le Foll
authors.forename: Munmun
authors.initials: M
authors.lastname: Chakraborty-Chatterjee
authors.forename: Shaul
authors.initials: S
authors.lastname: Lev-Ran
authors.forename: Chanel
authors.initials: C
authors.lastname: Barnes
authors.forename: Abhiram
authors.initials: A
authors.lastname: Pushparaj
authors.forename: Islam
authors.initials: I
authors.lastname: Gamaleddin
authors.forename: Yijin
authors.initials: Y
authors.lastname: Yan
authors.forename: Maram
authors.initials: M
authors.lastname: Khaled
authors.forename: Steven R
authors.initials: SR
authors.lastname: Goldberg
mesh_terms: D000818:Animals; D001552:Benzazepines / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects; D003463:Cues; D003627:Data Interpretation, Statistical; D004192:Discrimination, Psychological / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D058999:Drug-Seeking Behavior / Q000187:drug effects*; D005247:Feeding Behavior / Q000187:drug effects; D008297:Male; D009042:Motivation / Q000187:drug effects; D009538:Nicotine / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology*; D051381:Rats; D020318:Rats, Long-Evans; D017207:Rats, Sprague-Dawley; D012055:Reinforcement Schedule; D012646:Self Administration; D014029:Tobacco Use Disorder / Q000188:drug therapy* / Q000523:psychology; D000068580:Varenicline
chemical_list: D001552:Benzazepines; D011810:Quinoxalines; D009538:Nicotine; D000068580:Varenicline