EVIDENCE FOR INVOLVEMENT OF 5-HT1C AND 5-HT2 RECEPTORS IN THE FOOD-INTAKE SUPPRESSANT EFFECTS OF 1-(2,5-DIMETHOXY-4-IODOPHENYL)-2-AMINOPROPANE (DOI)

Administration of various doses of 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) to rats produced dose-related decreases in 1-h food intake in the food-deprived paradigm. Pretreatment with spiperone (5-HT1A/5-HT2/D2 antagonist), propranolol or CGP361A (beta-adrenoceptor antagonists that also have binding affinities for 5-HT1A and 5-HT1B sites) and MDL-72222 (5-HT3 antagonist) did not attenuate DOI-induced suppression of food intake. In contrast, pretreatment with metergoline (5-HT1/5-HT2 antagonist) completely blocked whereas mesulergine, mianserin and ritanserin (5-HT1c/5-HT2 antagonists) partially blocked DOI's effect on food intake. On the other hand, pretreatment with MDL-72222 but not with m-chlorophenylpiperazine (m-CPP) significantly potentiated DOI-induced suppression of food intake. Furthermore, the food intake suppressant effects of various doses of DOI were found to be similar in the Fawn-Hooded (FH) rat strain as compared to the Wistar rat strain. These findings suggest that DOI-induced suppression of food intake is mediated by stimulation of both 5-HT1C and 5-HT2 receptors.