Suppressing Effect of the Cannabinoid CB1 Receptor Antagonist, Rimonabant, on Alcohol Self-Administration in Alcohol-Preferring Rats

Abstract

Administration of the cannabinoid CB1 receptor antagonist, rimonabant (also known as SR 141716), has been reported to reduce alcohol intake (measured under the homecage 2-bottle "alcohol vs water" choice regimen) in selectively bred, Sardinian alcohol-preferring (sP) rats. The present study investigated whether rimonabant also had the capacity to decrease, in this rat line, alcohol's reinforcing properties. To this end, male sP rats were initially trained to lever-press (on a fixed ratio 4 schedule of reinforcement) to orally self-administer alcohol (15%, v/v) in daily 30-min sessions. Once lever-pressing and self-administration behaviors reached stable levels (150-200 responses/session and 0.8- 1 g/kg alcohol per session, respectively), the effect of rimonabant (0, 0.3, 1, and 3 mg/kg, i.p.) on responding for alcohol and amount of self-administered alcohol was determined. Pretreatment with rimonabant resulted in a significant, dose- dependent reduction in both variables; specifically, the total number of lever responses for alcohol and amount of self- administered alcohol in the rat groups treated with 0.3, 1, and 3 mg/kg rimonabant were approximately 20%, 35%, and 60% lower than those recorded in vehicle-treated rats. Pretreatment with 3 mg/kg rimonabant also resulted in a significant increase in the latency to the first response on the "alcohol" lever. These results demonstrate the capacity of rimonabant to suppress alcohol's reinforcing properties in alcohol-preferring sP rats. These data constitute a further piece of experimental evidence in support of the hypothesized role for the CB1 receptor in the control of alcohol drinking and reinforcement.