Suppressing effect of the cannabinoid CB1 receptor antagonist, SR147778, on alcohol intake and motivational properties of alcohol in alcohol-preferring sP rats.

Aims: The present study investigated the effect of the newly synthesized cannabinoid CB1 receptor antagonist, SR147778, on alcohol intake and alcohol's motivational properties in selectively bred Sardinian alcohol-preferring (sP) rats. Methods and Results: In Experiment 1, the repeated administration of SR147778 (0.3-3 mg/kg twice daily, i.p.) specifically suppressed the acquisition of alcohol drinking behaviour in alcohol-naive rats exposed to the 2-bottle "alcohol vs water" choice regimen for 24 hours/day. In Experiment 2, acutely administered SR147778 (2.5-10 mg/kg, i.p.) specifically reduced alcohol intake in alcohol-experienced rats given alcohol and water under the 2-bottle choice regimen in daily sessions of 4 hours. In Experiment 3, acutely administered SR147778 (0.3-3 mg/kg, i.p.) suppressed the "alcohol deprivation effect", i.e. the extra-intake of alcohol occurring after a period of alcohol abstinence. In Experiment 4, acutely administered SR147778 (0.3-3 mg/kg, i.p.) specifically suppressed the extinction responding for alcohol, i.e. the maximal number of lever responses reached in the absence of alcohol in rats trained to lever-press for alcohol (measure of alcohol's motivational properties). In Experiment 5, combination of 3 mg/kg SR147778 (i.p.) and 0.5 g/kg alcohol (i.p.), a dose comparable to those usually consumed by sP rats in each drinking binge, failed to induce any conditioned taste aversion. Conclusion: Taken together, these results extend to SR147778 the anti-alcohol profile of the prototype cannabinoid CB1 receptor antagonist, rimonabant (SR 141716), and strengthen the hypothesis that the cannabinoid CB1 receptor is part of the neural substrate mediating alcohol intake and alcohol's motivational properties.