Ethanol self-administration and ethanol conditioned place preference are reduced in mice lacking cannabinoid CB1 receptors

Cannabinoids are postulated to play a role in modulating the reinforcing effects of abused drugs, including alcohol. Experiment 1 examined alcohol self-administration in cannabinoid CB1 receptor knockout (KO), heterozygous (HT) and wild type (WT) mice in a two-bottle choice paradigm. Mice were trained in a limited 8 h access/day to 10% (v/v) EtOH (EtOH) versus water. After baseline drinking levels (% EtOH preference and total EtOH intake (g/kg)), results indicated that the CB1 knockout mice displayed significantly lower baseline EtOH consumption compared to wild type mice. Subsequently, treatment with SR141716A (5 mg/kg) significantly attenuated EtOH intake in the WT and HT mice but had little effect on the knockout mice. Experiment 2 examined the CB1 WT and CB1 KO strains in a conditioned place preference (CPP) procedure between saline and 2 g/kg EtOH. The CB1 WT mice spent significantly more time in the EtOH-paired versus saline-paired chambers, whereas no significant preference was observed in the CB1 KO mice. Finally, we observed that CB1 KO mice were significantly lighter than WT and HT and that SR141716A did not significantly alter body weight. These results demonstrate that the cannabinoid CB1 receptor is an essential component of the molecular pathways underlying the reinforcing effects of alcohol. Thus, medications targeting the CB1 receptors may be beneficial for the treatment of alcoholism.