One explanation for the lower ethanol preference of CB1 KO mice found in most studies may be due to increased sensitivity to its effects. Several labs have reported that CB1 KO mice display increased hypolocomotion, ataxia, hypothermia, and sleep time following acute injection with ethanol (Naassila et al., 2004; Racz et al., 2003; Vinod et al., 2008b; Warnault et al., 2007), and one study reported increased plasma ethanol concentration in CB1 mice following a high dose i.p. injection (5 g/kg) and forced pulmonary alcoholization (Lallemand and De Witte, 2005). It should be noted, however, that in this study and in others (Naassila et al., 2004; Warnault et al., 2007) differences in blood ethanol concentration (BEC) between genotypes were not observed with more moderate doses of ethanol suggesting that a null mutation of the CB1 gene produces only modest effects on ethanol metabolism. As a consequence of the numerous preclinical studies investigating the role of CB1 function in regulating ethanol consumption a clear picture emerges that activation of this receptor facilitates ethanol consumption while antagonism of CB1 reduces the motivational properties of ethanol perhaps by enhancing sensitivity to its other effects.
