Analysis of the 5-HT2 receptor ligands dimethoxy-4-indophenyl-2-aminopropane and ketanserin in ethanol discriminations.

Abstract

Previous studies have suggested a modulatory role of the 5-HT2 receptor system in the behavioral effects of ethanol. The present study examined the discriminative stimulus effects of the 5-HT2A/2C agonist (-)-dimethoxy-4-indophenyl-2-aminopropane (DOI) and the 5-HT2A antagonist ketanserin in rats trained to discriminate either 1.5 g/kg of ethanol from water (intragastrically, n = 7) or 2.0 g/kg of ethanol from water (intragastrically, n = 8). In substitution tests, neither DOI (0.3 to 1.0 mg/kg, i.p.) nor ketanserin (3.0 to 17.0 mg/kg, i.p.) produced discriminative stimulus effects similar to either training dose of ethanol, although decreases in rates of responding were significant at the highest doses tested. Likewise, when given in combination with ethanol, neither 5-HT2 ligand shifted the ethanol-dose response determination in either the 1.5 or 2.0 g/kg ethanol training groups. DOI in combination with ethanol did not alter rates of responding, whereas ketanserin in combination with ethanol significantly decreased response rates. Thus, the 5-HT2A receptor ligands do not appreciably affect the discriminative stimulus effects of ethanol, in contrast to previous results with 5-HT1B ligands.