Baclofen prevents drug-induced reinstatement of extinguished nicotine-seeking behaviour and nicotine place preference in rodents

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 baciofen 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 mu g/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. (C) 2009 Elsevier B.V. and ECNP. All rights reserved.