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The cannabinoid antagonist AM251 attenuates nicotine self-administration and nicotine-seeking behaviour in rats

Lookup NU author(s): Dr Mohammed Shoaib


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The cannabinoid receptor subtype (CB1) antagonist rimonabant (SR141716) has been shown to decrease nicotine self-administration and attenuate nicotine-evoked dopamine release in the nucleus accumbens; effects that support recent findings on its clinical efficacy as a smoking cessation aid. The present experiments aim to advance our understanding on the role of CB1 receptors in rodent models of nicotine dependence. AM251, a selective antagonist at CB1 receptors dose-dependently (1, 3 and 10 mg/kg IP) suppressed intravenous nicotine (0.03 mg/kg per infusion) self-administration in rats during three successive days of pre-treatment. This reduction was short lasting since behaviour was reinstated by suspending AM251 pre-treatment. This was relatively specific to nicotine self-administration since the profile of these reductions produced by AM251 was significantly different from the responses maintained by food pellets. In a model of nicotine-seeking behaviour, rats that had been extinguished by removal of nicotine and associated cues, and presented with a priming dose of nicotine (0.2 mg/kg SC) with the cues, showed robustly reinstated responses to nicotine-seeking behaviour. Acute pre-treatment with AM251 (1-10 mg/kg IP) dose-dependently attenuated the reinstatement effects produced by nicotine and the contingently presented cues. These preclinical findings support the use of rimonabant as a smoking cessation aid and highlight the CB1 receptor as a viable target to control intake of nicotine and prevent relapse. © 2007 Elsevier Ltd. All rights reserved.

Publication metadata

Author(s): Shoaib M

Publication type: Article

Publication status: Published

Journal: Neuropharmacology

Year: 2008

Volume: 54

Issue: 2

Pages: 438-444

ISSN (print): 0028-3908

ISSN (electronic): 1873-7064

Publisher: Pergamon


DOI: 10.1016/j.neuropharm.2007.10.011

PubMed id: 18054052


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