5-HT2 receptor antagonists do not reduce ethanol preference in Sardinian alcohol-preferring (sP) rats

The present study investigated the effect of the 5-HT2/1C receptor antagonist ritanserin, and of the 5-HT2/D2 receptor antagonist risperidone on ethanol preference in Sardinian alcohol-preferring (sP) rats. Rats were offered free access to both tap water and 8% (in one experiment 3%) ethanol solution. Subchronic (10 or 1 mg/kg/day, for 10 days) or chronic (1 mg/kg/day, for 30 days) subcutaneous (SC) ritanserin treatment failed to reduce 8% ethanol preference. Risperidone doses that produce marked 5-HT2, but low dopamine D2, receptor blockade (1 and 0.1 mg/kg/day, SC, for 9 and 10 days, respectively) did not modify 8% ethanol preference. On the other hand, a high risperidone dose (10 mg/kg/day, SC, for 14 days), which produces pronounced dopamine D2 receptor blockade, reduced 8% ethanol preference, like the dopamine receptor antagonist haloperidol. Previous studies have shown that both ritanserin and risperidone evoke long-lasting and pronounced suppression of 3% ethanol preference in genetically nonselected rats. However, in the present study, SC ritanserin treatment (1 mg/kg/day for 10 days) did not modify 3% ethanol preference in sP rats. The failure of 5-HT2 antagonists to reduce ethanol preference in sP rats raises the question whether genetic selection might have resulted in altered regulation of 5-HTergic mechanisms in sP rats.