In keeping with the concept that a genetic predisposition to ethanol abuse and dependence can arise from altered function of the EC system, C57BL/6 mice have a higher preference for ethanol and lower CB1 expression than DBA/2 mice (Hungund and Basavarajappa, 2000). In addition, rats bred selectively for high ethanol preference (AA rats) have decreased activity of FAAH and reduced CB1 expression in the prefrontal cortex compared to rats with low ethanol preference (Hansson et al., 2007). Furthermore, the AA phenotype can be reconstituted in non-selected rats by injecting the FAAH inhibitor, URB597, into the PFC. Similar results have been obtained in mice where genetic knockout of FAAH confers a higher preference for ethanol, and systemic treatment of wt mice with URB597 enhanced ethanol consumption (Basavarajappa et al., 2006; Blednov et al., 2007; Vinod et al., 2008a). FAAH KO mice also have reduced expression and function of CB1 in several brain regions including the dorsal striatum, NAc, and hippocampus (Vinod et al., 2008a). A consistent finding from these studies is that reduced FAAH activity is correlated with decreased expression of
