Ethanol induces higher BEC in CB1 cannabinoid receptor knockout mice while decreasing ethanol preference.

AIMS Previous studies have shown that CB(1) cannabinoid receptors are involved in the behavioural effects induced by chronic ethanol administration in Wistar rats by using SR 141716, a CB(1) cannabinoid receptor antagonist. These studies have now been extended to investigate the effect of acute and chronic alcoholization on blood ethanol concentration (BEC) and ethanol preference in CB(1) knockout (-/-) mice. METHODS BEC was monitored for a period of 8 h in both CB(1)(-/-) male mice and CB(1) male wild-type (+/+) mice, which had received an acute i.p. injection of ethanol in 1, 3 or 5 g/kg doses. Ethanol preference was assayed in both groups of male mice in non-forced ethanol administration and forced chronic pulmonary alcohol administration for 14 and 39 days, respectively. RESULTS After an acute intraperitoneal ethanol injection of 5 g/kg, CB(1)(-/-) mice showed a significant higher BEC during the ethanol elimination stage than the CB(1)(+/+) mice. However, those in the 1 and 3 g/kg groups showed no significant difference. A 2-3 fold increase in BEC was observed in CB(1)(-/-) mice on days 10 and 11 after commencement of forced chronic pulmonary alcoholization in comparison with CB(1)(+/+) mice, although comparable BEC values were assayed in both groups on day 12. In addition, these CB(1)(-/-) mice showed a significantly lower preference for ethanol than CB(1)(+/+) mice. CONCLUSIONS The studies on CB(1)(-/-) and CB(1)(+/+) mice have clearly confirmed the involvement of CB(1) receptor on ethanol induced behavioural effects and also revealed that CB(1) receptors may be implicated in ethanol absorption/distribution, particularly after administration of high ethanol doses.