that co-administration of ethanol and CB1 agonists may facilitate the neurotoxic effects of ethanol on neural tissue (Alén et al., 2010; Hansen et al., 2008). Interestingly, mice with a null mutation of DAGLα have reduced neurogenesis in the hippocampus (Gao et al., 2010). Co-administration of ethanol with a CB1 agonist is predicted to down-regulate cannabinoid signaling beyond that of ethanol administration alone, so the effects observed in DAGLα KO mice are in line with this effect. Additionally, these results suggest that the reduced neurogenesis observed in the ethanol-cannabinoid co-administration models may be mediated by reduced 2-AG signaling. It is important to note that all of these studies have employed non-contingent administration of the CB1 agonist, and this reduces the face validity of these studies for co-abuse models. Consequently, future studies should be performed using non-contingent ethanol administration paired with self-administration procedures for CB1 agonists in addition to studies employing contingent methods of drug delivery for both substances.
