ANALYSIS OF THE 5-HT2 RECEPTOR LIGANDS DIMETHOXY-4-INDOPHENYL-2-AMINOPROPANE AND KETANSERIN IN ETHANOL DISCRIMINATIONS

Previous studies have suggested a modulatory role of the 5-HT2 recepto r system in the behavioral effects of ethanol. The present study exami ned the discriminative stimulus effects of the 5-HT2A/2C agonist (-)-d imethoxy-4-indophenly-2-aminopropane (DOI) and the 5-HT2A antagonist k etanserin in mts trained to discriminate either 1.5 g/kg of ethanol fr om 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, ip) nor ketanserin (3.0 to 17.0 mg/kg, ip) produced discrimi native stimulus effects similar to either training dose of ethanol, al though decreases in rates of responding were significant at the highes t doses tested. Likewise, when given in combination with ethanol, neit her 5-HT2 ligand shifted the ethanol-dose response determination in ei ther the 1.5 or 2.0 g/kg ethanol training groups. DOI in combination w ith ethanol did not alter rates of responding, whereas ketanserin in c ombination with ethanol significantly decreased response rates. Thus, the 5-HT2A receptor ligands do not appreciably affect the discriminati ve stimulus effects of ethanol, in contrast to previous results with 5 -HT1B ligands.