The goal of all addiction therapies is to prevent a relapse to binge use, and given the EC system’s association with ethanol reward, consumption, and withdrawal processes, it is logical to assume that this neuromodulatory system is involved in the mechanisms underlying relapse. Data supporting of the involvement of CB1 in relapse have been obtained primarily from reinstatement models of ethanol self-administration in rodents where CB1 agonists facilitate reinstatement and CB1 antagonists block it. Several studies have reported that non-contingent administration of WIN during abstinence facilitates the subsequent reinstatement to ethanol responding (Alén et al., 2009; López-Moreno et al., 2004), and this increase in ethanol-seeking behavior is correlated with reduced hippocampal neurogenesis (Alén et al., 2010). Furthermore, sub-chronic administration of WIN reduces the DA response in the NAc shell to a subsequent dose of ethanol administered 24 hrs later, and these effects may be compounded by similar reductions observed after chronic treatment with ethanol (Lopez-Moreno et al., 2008). These data suggest that the enhancement of ethanol-seeking following the administration of CB1 agonists during periods of abstinence may be due to
