title: Varenicline effects on cocaine self administration and reinstatement behavior.
abstract: This study tested the effects of the nicotine addiction treatment varenicline on cocaine self administration (SA) and reinstatement. In one SA experiment, rats were trained to self-administer cocaine (0.75 mg/kg/infusion). Thereafter, daily SA sessions continued as before except that every fourth session was preceded by a presession injection of varenicline (0.0, 0.3, 1.0 and 2.0 mg/kg, SC, 50-min presession). In three reinstatement experiments, animals were exposed sequentially to SA training, extinction training, and several reinstatement test sessions. In two of the reinstatement experiments, cocaine-seeking was reinstated by presentation of cocaine-predictive cues at the onset of the test session (cue reinstatement). In a third reinstatement experiment, cocaine-seeking was reinstated by a presession injection of cocaine (drug reinstatement). Each reinstatement session was preceded by an injection of either vehicle or varenicline (dose range of 0.1-2.0 mg/kg). The SA and reinstatement experiments showed that low-dose varenicline decreases reinstatement behavior, without significantly affecting cocaine SA. In contrast, high-dose varenicline increases reinstatement of cocaine-directed behavior and decreases cocaine SA. A control study showed that sucrose-directed behavior is unaltered by varenicline. On the basis of these findings, low-varenicline doses might decrease relapse in cocaine-addicted individuals, but high doses of varenicline might have the opposite effect.
authors.affiliation: Department of Integrative Neurophysiology, CNCR, VU University, Amsterdam, The Netherlands.
authors.forename: Karine
authors.initials: K
authors.lastname: Guillem
authors.forename: Laura L
authors.initials: LL
authors.lastname: Peoples
mesh_terms: D000818:Animals; D016739:Behavior, Addictive / Q000188:drug therapy*; D001552:Benzazepines / Q000627:therapeutic use*; D003042:Cocaine / Q000008:administration & dosage / Q000037:antagonists & inhibitors*; D003216:Conditioning, Operant / Q000187:drug effects; D003463:Cues; D005108:Extinction, Psychological / Q000187:drug effects; D008297:Male; D018722:Nicotinic Agonists / Q000627:therapeutic use*; D011810:Quinoxalines / Q000627:therapeutic use*; D051381:Rats; D020318:Rats, Long-Evans; D055502:Secondary Prevention; D012646:Self Administration; D000068580:Varenicline
chemical_list: D001552:Benzazepines; D018722:Nicotinic Agonists; D011810:Quinoxalines; D003042:Cocaine; D000068580:Varenicline