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

V. Warnault, H. Houchi, E. Barbier, O. Pierrefiche, C. Vilpoux et al.

Université de Picardie Jules Verne, Groupe de Recherche sur l’Alcool et les Pharmacodépendances (GRAP), Equipe Région INSERM 24 (ERI24), Amiens, France.

Journal of Neurochemistry

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. GABAA_1, _2, and _2 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.

BIOSEB Instruments Used:
Infrared Actimeter (LE8815)

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