title: Baclofen prevents drug-induced reinstatement of extinguished nicotine-seeking behaviour and nicotine place preference in rodents.
abstract: The gamma-aminobutyric acid(GABA)-B receptor agonist baclofen is known to reduce drug intake in both animals and humans and to prevent reinstatement of cocaine-, opioid-, and alcohol-seeking in rats after a period of extinction, but its effect on nicotine reinstatement is unknown. This study investigated the effect of baclofen on nicotine-seeking reinstatement both using the extinction/reinstatement model of nicotine self-administration and conditioned place preference (CPP). Results showed that in rats previously trained to intravenously self-administer nicotine (30 microg/kg/inf) under a FR-1 schedule of reinforcement, acute nicotine (0.15 mg/kg) priming effectively reinstates nicotine-seeking behaviour following extinction. At doses used in this study (up to 2.5 mg/kg) baclofen alone did not affect locomotor activity and did not reinstate responding. However, baclofen dose-dependently attenuated drug-induced reinstatement of nicotine-seeking in rats. Moreover, baclofen (1.25 mg/kg) completely blocked nicotine-induced reinstatement of extinguished nicotine (0.3 mg/kg) CPP in mice. Altogether, our results showed that baclofen is able to antagonise reinstatement of nicotine-seeking and CPP triggered by nicotine primings, suggesting its potential clinical utility as an anti-relapse agent.
authors.affiliation: Institute of Neuroscience, Section of Cagliari, National Research Council CNR, c/o Department of Neuroscience, University of Cagliari, Cittadella Universitaria of Monserrato, Italy. lfattore@in.cnr.it
authors.forename: Liana
authors.initials: L
authors.lastname: Fattore
authors.forename: Maria Sabrina
authors.initials: MS
authors.lastname: Spano
authors.forename: Gregorio
authors.initials: G
authors.lastname: Cossu
authors.forename: Maria
authors.initials: M
authors.lastname: Scherma
authors.forename: Walter
authors.initials: W
authors.lastname: Fratta
authors.forename: Paola
authors.initials: P
authors.lastname: Fadda
mesh_terms: D000818:Animals; D001418:Baclofen / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D003216:Conditioning, Operant / Q000187:drug effects*; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D005108:Extinction, Psychological / Q000187:drug effects*; D018755:GABA Agonists / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009538:Nicotine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012055:Reinforcement Schedule; D012054:Reinforcement, Psychology; D012646:Self Administration / Q000379:methods; D014029:Tobacco Use Disorder / Q000523:psychology*
chemical_list: D018755:GABA Agonists; D009538:Nicotine; D001418:Baclofen