Decreased alcohol self-administration and increased alcohol sensitivity and withdrawal in CB1 receptor knockout mice.
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.
Naassila
Mickaël
M
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
Pierrefiche
Olivier
O
Ledent
Catherine
C
Daoust
Martine
M
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*
D043884:Receptor, Cannabinoid, CB1; D000431:Ethanol