Effects of a 5-HT3 antagonist on peripheral 5-hydroxytryptamine-induced anorexia

Abstract

Since antagonizing peripheral5-HT 2 receptors incompletely blocks the anorexia induced by systemically administered 5-HT, another 5-HT receptor subtype is implicated in this effect. To determine whether the 5-HT3 receptor is the additional type involved, the specific, peripheral5-HT 3 antagonist [[3-(l-Methyl-lH-indol-3-yl)-1,2,4-oxadiazol-5-yl]methyl]trimethyl-ammonium iodide (MIO) was used. After an overnight fast, rats were ir\iected with MIO followed 1 h later by 5 mg/kg of 5-HT. There was a dose-dependent potentiation by MIO of the 5-HT-induced anorexia that peaked at a dose of 2.5 mg/kg of MIO. However, MIO by itself failed to induce an anorexia. Although the 5-HT3 receptor is implicated in 5-HT-induced anorexia, it is suggested that its activation counters the effects of 5-HT in the mediation of the anorexia.