Nicotine reinforcement is reduced by cannabinoid CB1 receptor blockade in the ventral tegmental area

Authors

  • Amelie Simonnet,

    1. Institut de Neurosciences Cognitives et Integratives d'Aquitaine, Neuropsychopharmacologie de l'Addiction, Universite Bordeaux, Bordeaux, France
    2. Institut de Neurosciences Cognitives et Integratives d'Aquitaine, CNRS UMR5287, Bordeaux, France
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  • Martine Cador,

    1. Institut de Neurosciences Cognitives et Integratives d'Aquitaine, Neuropsychopharmacologie de l'Addiction, Universite Bordeaux, Bordeaux, France
    2. Institut de Neurosciences Cognitives et Integratives d'Aquitaine, CNRS UMR5287, Bordeaux, France
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  • Stephanie Caille

    Corresponding author
    1. Institut de Neurosciences Cognitives et Integratives d'Aquitaine, Neuropsychopharmacologie de l'Addiction, Universite Bordeaux, Bordeaux, France
    2. Institut de Neurosciences Cognitives et Integratives d'Aquitaine, CNRS UMR5287, Bordeaux, France
    • Correspondence to: Stephanie Caille, University of Bordeaux, CNRS UMR5287, BP31 146 rue Leo Saignat, 33000 Bordeaux, France. E-mail: stephanie.garnier@u-bordeaux2.fr

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Abstract

Cannabinoid type 1 (CB1) receptors control the motivational properties and reinforcing effects of nicotine. Indeed, peripheral administration of a CB1 receptor antagonist dramatically decreases both nicotine taking and seeking. However, the neural substrates through which the cannabinoid CB1 receptors regulate the voluntary intake of nicotine remain to be elucidated. In the present study, we sought to determine whether central injections of a CB1 receptor antagonist delivered either into the ventral tegmental area (VTA) or the nucleus accumbens (NAC) may alter nicotine intravenous self-administration (IVSA). Rats were first trained to self-administer nicotine (30 μg/kg/0.1 ml). The effect of central infusions of the CB1 antagonist AM 251 (0, 1 and 10 μg/0.5 μl/side) on nicotine-taking behavior was then tested. Intra-VTA infusions of AM 251 dose dependently reduced IVSA with a significant decrease for the dose 10 μg/0.5 μl/side. Moreover, operant responding for water was unaltered by intra-VTA AM 251 at the same dose. Surprisingly, intra-NAC delivery of AM 251 did not alter nicotine behavior at all. These data suggest that in rats chronically exposed to nicotine IVSA, the cannabinoid CB1 receptors located in the VTA rather than in the NAC specifically control nicotine reinforcement and, subsequently, nicotine-taking behavior.

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