Suppression of alcohol preference in rats induced by risperidone, a serotonin 5-HT2 and dopamine D2 receptor antagonist.

The present study investigated the effect of the 5-HT2 and dopamine D2 receptor antagonist risperidone on alcohol preference in the rat. Rats with developed preference for 3% ethanol were injected subcutaneously (SC) with 10, 1, or 0.1 mg/kg of risperidone for 7, 10, and 10 days, respectively. Risperidone (10 mg/kg) evoked an inhibitory effect on alcohol preference similar (rapid onset, but short duration) to that observed after treatment with the dopamine D2 receptor antagonist haloperidol, 0.0625 mg/kg, SC. The lowest dose of risperidone (0.1 mg/kg) evoked marked inhibition of ethanol drinking, similar (slow onset, but long-lasting effect) to that produced by the 5-HT2 receptor antagonist ritanserin, 1 mg/kg, SC. Present results demonstrate that risperidone suppresses alcohol preference in the rat and suggest that its effect, depending on the dose, might involve different neurochemical mechanisms (mainly dopaminergic at high doses and mainly serotonergic at low doses). The results obtained with the lowest dose of risperidone (0.1 mg/kg), at which the drug is rather selective for 5-HT2 receptors, are in keeping with previous findings obtained with ritanserin and support the hypothesis that 5-HT2 receptor blockade reduces alcohol intake in rats.