SUPPRESSING EFFECT OF THE CANNABINOID CB1 RECEPTOR ANTAGONIST, SR147778, ON ALCOHOL INTAKE AND MOTIVATIONAL PROPERTIES OF ALCOHOL IN ALCOHOL-PREFERRING sP RATS

Abstract

Aims: The present study investigated the effect of the newly synthesized cannabinoid CB₁ receptor antagonist, SR147778, on alcohol intake and the motivational properties of alcohol 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 two-bottle ‘alcohol vs water’ choice regimen for 24 h/day. In Experiment 2, an acute administration of SR147778 (2.5–10 mg/kg, i.p.) specifically reduced alcohol intake in alcohol-experienced rats that were given alcohol and water under the two-bottle choice regimen in daily sessions of 4 h. In Experiment 3, an acute administration of 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, an acute administration of 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 the motivational properties of alcohol). In Experiment 5, the combination of 3 mg/kg of SR147778 (i.p.) and 0.5 g/kg of alcohol (i.p.), a dose comparable with 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 (SR141716), and strengthen the hypothesis that the cannabinoid CB₁ receptor is part of the neural substrate mediating alcohol intake and the motivational properties of alcohol.