Effects of the atypical antipsychotic remoxipride on alcohol self-administration

Remoxipride is a dopamine (DA) D2 antagonist that produces fewer of the side effects normally associated with chronic DA antagonist administration. It has been demonstrated that DA antagonists can reduce the desire for a second drink in alcoholics. However, because of the usual side effects associated with DA antagonist administration, chronic use as an adjunct to alcoholism treatment has not been considered. Because the DA D2 antagonist haloperidol reduces ethanol self-administration in an operant animal model of ethanol self-administration, this study was designed to determine whether remoxipride would produce similar results. Six Long-Evans rats were initiated to self-administer ethanol in daily 30-min operant sessions using a sucrose-substitution procedure. Following establishment of ethanol-reinforced lever pressing, remoxipride (0.5, 1.0, 5.0, or 10.0 mg/kg) or haloperidol (0.01, 0.05, or 0.1 mg/kg) were injected 30 min prior to the sessions. Remoxipride produced an approximate 50% reduction in the number of ethanol presentations per session at the highest dose tested (10.0 mg/kg) and did so by terminating the ethanol-drinking bout earlier in the session. Haloperidol also decreased ethanol presentations with the highest dose tested (0.1 mg/kg) producing the largest effect. These data indicate that remoxipride produces reductions in ethanol-reinforced responding similar to those observed with another DA antagonist. Because remoxipride produces fewer of the side effects commonly observed with chronic DA antagonist administration, it could prove to be a useful adjunct in the treatment of excessive alcohol consumption.