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

Aims: Previous studies have shown that CB1 cannabinoid receptors are involved in the behavioural effects induced by chronic ethanol administration in Wistar rats by using SR 141716, a CB1 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 CB1 knockout (-/-) mice. Methods: BEC was monitored for a period of 8 h in both CB1-/- male mice and CB1 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, CB1-/- mice showed a significant higher BEC during the ethanol elimination stage than the CB1+/+ 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 CB1-/- mice on days 10 and 11 after commencement of forced chronic pulmonary alcoholization in comparison with CB1+/+ mice, although comparable BEC values were assayed in both groups on day 12. In addition, these CB1-/- mice showed a significantly lower preference for ethanol than CB1+/+ mice. Conclusions: The studies on CB1-/- and CB1+/+ mice have clearly confirmed the involvement of CB1 receptor on ethanol induced behavioural effects and also revealed that CB1 receptors may be implicated in ethanol absorption/distribution, particularly after administration of high ethanol doses.