Distinct differences in the cannabinoid receptor binding in the brain of C57BL/6 and DBA/2 mice, selected for their differences in voluntary ethanol consumption

The two inbred strains of mice C57BL/6 and DBA/2 mice have been shown to differ significantly in their preference for alcohol (EtOH). These strains of mice have been employed to study various aspects of pharmacological and behavioral effects of EtOH. We have previously demonstrated that chronic EtOH exposure down-regulated cannabinoid receptors (CB1) in mouse synaptic plasma membranes and enhanced the synthesis of endogenous cannabimimetic compound anandamide (AnNH) in human neuroblastoma cells. The purpose of the present study was to investigate whether there were differences in the density and the affinity of CB1 receptors in the brains of the two inbred C57BL/6 (alcohol-preferring) and DBA/2 (alcohol avoiding) mice. The results indicate the presence of specific CB1 receptors in the brain membranes of both the strains. It was also found that the CB1 receptor densities (B(max)) were 25% lower in C57BL/6 (0.66 +/- 0.15 pmol/mg protein) compared with that of DBA/2 (0.88 +/- 0.08 pmol/mg protein) mice. Significant differences in the affinity were also observed between the two lines (K(d), 0.68 +/- 0.15 nM for C57BL/6 and 2.21 +/- 0.56 nM for DBA/2). The competition studies with SR141716A, a CB1 receptor antagonist, and 2-arachidonylglycerol (2-AG) and anandamide (AnNH), known CB1 receptor agonists, all showed a substantial decrease in [(3)H]CP-55,940 binding in both strains of mice with a higher K(i) values in the DBA/2 mice. These results suggest that CB1 receptor signal transduction may play an important role in controlling the voluntary EtOH consumption by these strains of mice.