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Monday, March 19, 2007

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

Journal of Neurochemistry (OnlineAccepted Articles).
12 March 2007

  • *Equipe Région INSERM 24 (ERI24), Groupe de Recherche sur l'Alcool et les Pharmacodépendances (GRAP), Université de Picardie Jules Verne, Faculté de Pharmacie, 1 rue des Louvels, Amiens, France; +Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire (IRIBHM), Université libre de Bruxelles, Bât C, Bruxelles, Belgium.
* 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, 80000 Amiens, France, Tél: +33 3 22 82 77 58, Fax: +33 3 22 82 76 72. E-mail: mickael.naassila@u-picardie.fr

Abstract

Because the contribution of 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 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.

GABAA α1, β2, γ2 and NMDA NR1, NR2B 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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