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The lack of CB1 receptors prevents neuroadapatations of both NMDA and GABA(A) receptors after chronic ethanol exposure.
Warnault V., Houchi H., Barbier E., Pierrefiche O., Vilpoux C., Ledent C., Daoust M., Naassila M.
Journal of Neurochemistry 102, 3 (2007) 741-52 - http://www.hal.inserm.fr/inserm-00746175
The lack of CB1 receptors prevents neuroadapatations of both NMDA and GABA(A) receptors after chronic ethanol exposure.
Vincent Warnault1, Hakim Houchi1, Estelle Barbier1, Olivier Pierrefiche1, Catherine Vilpoux1, Catherine Ledent1, Martine Daoust1, Mickaël Naassila1
1 :  Alcoolisation précoce et vulnerabilité à la dépendance
INSERM : ERI24 – Université de Picardie Jules Verne
faculte de pharmacie 1, rue des louvels 80037 AMIENS CEDEX 1
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 GABA(A) receptors in CB1-/- mice. Our results show that basal levels of hippocampal [(3)H]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 [(3)H]muscimol binding was lower and sensitivity to the hypothermic effects of diazepam and pentobarbital was increased in CB1-/- mice. GABA(A)alpha1, beta2, and gamma2 and NMDA receptor (NR) 1 and 2B subunit mRNA levels were altered in striatum of CB1-/- mice. Our results also showed that [(3)H]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 [(3)H]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 GABA(A) receptors after chronic ethanol exposure and that the endocannabinoid/CB1 receptor system is involved in alcohol dependence.
Sciences du Vivant/Neurosciences

Articles dans des revues avec comité de lecture
Journal of Neurochemistry (J Neurochem)
Publisher Wiley-Blackwell
ISSN 0022-3042 (eISSN : 1471-4159)

Adaptation – Physiological – Alcohol-Induced Disorders – Nervous System – Alcoholism – Animals – Binding Sites – Binding – Competitive – Brain – Brain Chemistry – Chronic Disease – Disease Models – Animal – Dose-Response Relationship – Drug – Ethanol – Excitatory Amino Acid Antagonists – GABA Agonists – Male – Mice – Knockout – Muscimol – Protein Subunits – RNA – Messenger – Receptor – Cannabinoid – CB1 – Receptors – GABA-A – N-Methyl-D-Aspartate