Effects of CB1 cannabinoid receptor blockade on ethanol preference after chronic alcohol administration combined with repeated re-exposures and withdrawals

Abstract

Aims: The cannabinoid CB1 receptor antagonist, SR141716A, differentially affects the ethanol preference of chronically alcoholized rats when administered during cycles of ethanol exposure and withdrawal. In this study, ethanol preference was investigated in chronically alcoholized rats that underwent regular withdrawal periods during which the brain cannabinoid CB1 receptor antagonist, SR141716A, was administered. Methods: The cannabinoid receptor antagonist SR141716A, 3 or 10 mg/kg/day, was administered i.p. to Wistar rats at the conclusion of a 4-week period of chronic alcoholization, as they commenced a cycle of alcohol withdrawal for 10 days followed by a period of 10 days chronic ethanol exposure. In a second set of experiments, an additional cycle of ethanol withdrawal and re-exposure was given. Preference for ethanol versus water started at the end of the first or second chronic ethanol re-exposure for a period of at least 30 days. Results: In rats pretreated with the higher dose of SR141716A, ethanol preference during free choice was significantly increased after two ethanol re-exposures. In contrast, pretreatment with the lower SR141716A dose induced no significant change in ethanol intake during the free choice followed by either one or two ethanol re-exposures. Conclusions: SR141716A, 10 mg/kg/day dose, induced a significant increase in ethanol preference which was dependent on both the number of ethanol withdrawals and chronic ethanol re-exposures, while 3 mg/kg/day had no significant effect on ethanol preference. © Medical Council on Alcohol 2004; all rights reserved.