The lack of CB1 receptors prevents neuroadapatations of both NMDA and GABAA receptors after chronic ethanol exposure

Authors

  • Vincent Warnault,

    1. Equipe Région INSERM 24 (ERI24), Groupe de Recherche sur l’Alcool et les Pharmacodépendances (GRAP), Université de Picardie Jules Verne, Faculté de Pharmacie, Amiens, France and IFR 114 Lille
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  • Hakim Houchi,

    1. Equipe Région INSERM 24 (ERI24), Groupe de Recherche sur l’Alcool et les Pharmacodépendances (GRAP), Université de Picardie Jules Verne, Faculté de Pharmacie, Amiens, France and IFR 114 Lille
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  • Estelle Barbier,

    1. Equipe Région INSERM 24 (ERI24), Groupe de Recherche sur l’Alcool et les Pharmacodépendances (GRAP), Université de Picardie Jules Verne, Faculté de Pharmacie, Amiens, France and IFR 114 Lille
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  • Olivier Pierrefiche,

    1. Equipe Région INSERM 24 (ERI24), Groupe de Recherche sur l’Alcool et les Pharmacodépendances (GRAP), Université de Picardie Jules Verne, Faculté de Pharmacie, Amiens, France and IFR 114 Lille
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  • Catherine Vilpoux,

    1. Equipe Région INSERM 24 (ERI24), Groupe de Recherche sur l’Alcool et les Pharmacodépendances (GRAP), Université de Picardie Jules Verne, Faculté de Pharmacie, Amiens, France and IFR 114 Lille
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  • Catherine Ledent,

    1. Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire (IRIBHM), Université libre de Bruxelles, Bruxelles, Belgium
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  • Martine Daoust,

    1. Equipe Région INSERM 24 (ERI24), Groupe de Recherche sur l’Alcool et les Pharmacodépendances (GRAP), Université de Picardie Jules Verne, Faculté de Pharmacie, Amiens, France and IFR 114 Lille
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  • Mickaël Naassila

    1. Equipe Région INSERM 24 (ERI24), Groupe de Recherche sur l’Alcool et les Pharmacodépendances (GRAP), Université de Picardie Jules Verne, Faculté de Pharmacie, Amiens, France and IFR 114 Lille
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Address correspondence and reprint requests to Dr M Naassila, Equipe Région INSERM 24 (ERI 24), Groupe de Recherche sur l’Alcool et les Pharmacodépendances (GRAP), Université de Picardie Jules Verne, Faculté de Pharmacie, 1 rue des Louvels, Amiens 80000, France. E-mail: mickael.naassila@u-picardie.fr

Abstract

As the contribution of cannabinoid (CB1) receptors in the neuroadaptations following chronic alcohol exposure is unknown, we investigated the neuroadaptations induced by chronic alcohol exposure on both NMDA and GABAA receptors in CB1−/− mice. Our results show that basal levels of hippocampal [3H]MK-801 ((1)-5-methyl-10,11-dihydro-5Hdibenzo[a,d]cyclohepten-5,10-imine) binding sites were decreased in CB1−/− mice and that these mice were also less sensitive to the locomotor effects of MK-801. Basal level of both hippocampal and cerebellar [3H]muscimol binding was lower and sensitivity to the hypothermic effects of diazepam and pentobarbital was increased in CB1−/− mice. GABAAα1, β2, and γ2 and NMDA receptor (NR) 1 and 2B subunit mRNA levels were altered in striatum of CB1−/− mice. Our results also showed that [3H]MK-801 binding sites were increased in cerebral cortex and hippocampus after chronic ethanol ingestion only in wild-type mice. Chronic ethanol ingestion did not modify the sensitivity to the locomotor effects of MK-801 in both genotypes. Similarly, chronic ethanol ingestion reduced the number of [3H]muscimol binding sites in cerebral cortex, but not in cerebellum, only in CB1+/+ mice. We conclude that lifelong deletion of CB1 receptors impairs neuroadaptations of both NMDA and GABAA receptors after chronic ethanol exposure and that the endocannabinoid/CB1 receptor system is involved in alcohol dependence.

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