Long-lasting suppression of alcohol preference in rats following serotonin receptor blockade by ritanserin

Rats with developed preference for 3% ethanol were injected subcutaneously (SC) with 10 mg/kg of the 5HT2 antagonist ritanserin for 9 days. This resulted in a marked and significant suppression of alcohol preference, as compared to controls. The effect was very long-lasting, as shown by the fact that it was still evident up to 20 days after the end of the treatment. Since ritanserin shows some affinity also for D2-dopaminergic receptors (even though much lower than for 5HT2 receptors), for comparison, other rats were injected SC for 9 days with 0.0625 mg/kg of haloperidol or with its vehicle. The effect of haloperidol treatment was low and short-lasting. Depletion of endogenous serotonin by p-chlorophenylalanine (600 mg/kg x 3 days) completely abolished the suppression of alcohol preference by ritanserin. These results suggest that: 1) the ritanserin-induced reduction of alcohol preference is not due to dopaminergic blockade, 2) that the effect of ritanserin is completely dependent on the endogenous serotoninergic mechanisms.