Abstract
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 \(\mathrm{CB}_{1}^{{-}/{-}}\) 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, \(\mathrm{CB}_{1}^{{-}/{-}}\) mice showed a significant higher BEC during the ethanol elimination stage than the \(\mathrm{CB}_{1}^{+/+}\) 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 \(\mathrm{CB}_{1}^{{-}/{-}}\) mice on days 10 and 11 after commencement of forced chronic pulmonary alcoholization in comparison with \(\mathrm{CB}_{1}^{+/+}\) mice, although comparable BEC values were assayed in both groups on day 12. In addition, these \(\mathrm{CB}_{1}^{{-}/{-}}\) mice showed a significantly lower preference for ethanol than \(\mathrm{CB}_{1}^{+/+}\) mice. Conclusions: The studies on \(\mathrm{CB}_{1}^{{-}/{-}}\) and \(\mathrm{CB}_{1}^{+/+}\) 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.