Effects of remoxipride, an atypical antipsychotic, on cocaine self-administration in the rat using fixed- and progressive-ratio schedules of reinforcement

Remoxipride, a selective D2-dopamine receptor antagonist with preferential activity for mesolimbic-mediated behaviors, was assessed for its potential to block cocaine self-administration. The effects of remoxipride (RMX) were evaluated using fixed-ratio-1 (FR-1) and progressive-ratio (PR) schedules of reinforcement. On FR-1, RMX pretreatment increased the rate of cocaine injections, while on a PR, breaking points were reduced. Daily RMX treatment also resulted in breaking point reductions, but the decreases in cocaine's reinforcing potency did not result in extinction of cocaine intake and were not sustained upon cessation of RMX. Thus, RMX can reduce the rewarding effects of cocaine, and if safely tolerated over sustained periods of treatment it, or drugs with a similar pharmacological profile, could provide a therapeutic adjunct in the treatment of cocaine addiction.