SR blocks the increased firing rate observed after acute ethanol administration (Perra et al., 2005). Consistent with these findings, CB1 KO mice lack the increase in NAc DA concentrations observed in wt mice following an acute injection of ethanol (Hungund et al., 2003), and CB1 KO mice also display blunted conditioned place preference for ethanol (Houchi et al., 2005). Data from humans also implicates a polymorphism in the CNR1 gene in modulating the reinforcing properties of ethanol (Hutchison et al., 2008). Together, these studies support the hypothesis that the rewarding properties of ethanol are produced in part by the EC-mediated facilitation of VTA DA neuron activation, and they suggest that genetic differences in CB1 signaling and expression may predispose some individuals to abuse and dependence.
