1-(2,5-Dimethoxy-4-iodophenyl)-2-aminopropane (DOI) exerts an anorexic action that is blocked by 5-HT2 antagonists in rats

Previous literature suggests that the anorexic action of peripherally administered serotonin (5-HT) is mediated by 5-HT₂ receptors. This study, therefore, examined the effect of DOI, a non-indole 5-HT₂ agonist, on deprivation-induced feeding. Rats were first adapted to a schedule in which a milk diet was presented for 6 h daily. Intraperitoneal (IP) administration of DOI (1.0–11.2 mol/kg) inhibited feeding in a dose-related fashion (ID₅₀=2.6 mol/kg). One hour pretreatment with 6.0 mol/kg of the 5-HT₂ antagonists ketanserin and LY53857 completely reversed the anorexic action of an equimolar dose of DOI. Neither ketanserin nor LY53857, alone, altered baseline feeding. Further testing demonstrated the antagonistic effect of LY53857 (0.047–6.0 mol/kg, IP) to be dose related, with an ID₅₀ of 0.14 mol/kg. Ten minute pretreatment with 1-(1-naphthyl)-piperazine (1-NP; 2.0 or 4.0 mol/kg), a mixed-acting agent with 5HT₂ blocking actions, also attenuated the anorexic effect of 6.0 mol/kg DOI. Unlike ketanserin and LY53857, however, 1-NP did reduce food intake by itself. By contrast with ketanserin, LY53857 and 1-NP, the peripherally-acting 5-HT₂ antagonist xylamidine failed to alter the anorexic effect of DOI. Taken together, these results suggest that central 5-HT₂ receptors are important in the control of ingestive behavior.A portion of these results were presented in a preliminary report at the Annual Meeting of the Society for Neuroscience in November 1987.