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Alcohol and Alcoholism Advance Access published online on November 18, 2004
Alcohol and Alcoholism, doi:10.1093/alcalc/agh115
© 2004 by Medical Council on Alcohol
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Received August 6, 2004
Revised September 17, 2004
Accepted October 1, 2004

Special Issue Article

ETHANOL INDUCES HIGHER BEC IN CB1 CANNABINOID RECEPTOR KNOCKOUT MICE WHILE DECREASING ETHANOL PREFERENCE

F. LALLEMAND 1 and P. DE WITTE 1*

1 Biologie du Comportement, Université Catholique de Louvain, 1 Place Croix du Sud, 1348 Louvain-la-Neuve, Belgium

* To whom correspondence should be addressed.
P. DE WITTE, E-mail: dewitte{at}bani.ucl.ac.be


  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 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.


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