title: Decreased alcohol self-administration and increased alcohol sensitivity and withdrawal in CB1 receptor knockout mice.
abstract: Recent advances in the understanding of the neurobiological basis of alcohol dependence suggest that the endocannabinoid system may play a key role in the reinforcing effects of ethanol. In the present study, disruption of CB1 receptors in mice generated on a CD1 background decreased both ethanol consumption and preference. This decreased ethanol self-administration was associated with increased sensitivity to the acute intoxicating effects of ethanol. Mutant mice were more sensitive to the hypothermic and sedative/hypnotic effects of acute ethanol administration (1.5-4.0 g/kg), although plasma ethanol concentrations did not differ from those of controls. Moreover, wild-type mice exhibited normal locomotor activation caused by 1.0-2.5 g/kg injection of ethanol, whereas mutant mice displayed sedation in response to the injection of the same ethanol doses. The severity of alcohol withdrawal-induced convulsions was also increased in CB1(-/-) mice. Our results suggest that CB1 receptors participate in the regulation of ethanol drinking and demonstrate that their disruption lead to increased ethanol sensitivity and withdrawal severity.
authors.affiliation: EA2088 ETP-APC Environnement Toxique Périnatal-Adaptations Physiologiques et Comportementales, Université de Picardie Jules Verne, Faculté de Pharmacie, 1 rue des Louvels, 80000 Amiens, France. mickael.naassila@u-picardie.fr
authors.forename: Mickaël
authors.initials: M
authors.lastname: Naassila
authors.forename: Olivier
authors.initials: O
authors.lastname: Pierrefiche
authors.forename: Catherine
authors.initials: C
authors.lastname: Ledent
authors.forename: Martine
authors.initials: M
authors.lastname: Daoust
mesh_terms: D000428:Alcohol Drinking / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000008:administration & dosage*; D005260:Female; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D043884:Receptor, Cannabinoid, CB1 / Q000172:deficiency* / Q000235:genetics; D012646:Self Administration / Q000379:methods; D013375:Substance Withdrawal Syndrome / Q000235:genetics / Q000378:metabolism*
chemical_list: D043884:Receptor, Cannabinoid, CB1; D000431:Ethanol