Melatonin reversal of DOI-induced hypophagia in rats; possible mechanism by suppressing 5-HT2A receptor-mediated activation of HPA axis

Serotonin type 2A (5-HT2A) receptor-mediated neurotransmitter is known to a ctivate hypotholamic-pituitary-adrenal (HPA) axis, regulate sleep-awake cyc le, induce anorexia and hyperthermia. Interaction between melatonin and 5-H T2A receptors in the regulation of the sleep-awake cycle and head-twitch re sponse in rat have been reported. Previous studies have shown that melatoni n has suppressant effect on HPA axis activation, decreases core body temper ature and induces hyperphagia in animals. However, melatonin interaction wi th 5-HT2A receptors in mediation of these actions is not yet reported. We h ave studied the acute effect of melatonin and its antagonist, luzindole on centrally administered(+/-)-1-(2,5-dimethoxy-4-iodophenyl) 2-amino propane (DOI: a 5-HT2A/2C agonist)-induced activation of HPA axis, hypophagia and h yperthermia in 24-h food-deprived rats. Like ritanserin [(1 mg/kg, i.p.) 5- HT2A/2C antagonist], peripherally administered melatonin (1.5 and 3 mg/kg, i.p.) did not affect the food intake, rectal temperature or basal adrenal a scorbic acid level. However, pretreatment of rats with it significantly rev ersed DOI (10 mu g, intraventricular)-induced anorexia and activation of HP A axis. But the hyperthermia induced by DOI was not sensitive to reversal b y melatonin. Mel(1) receptor subtype antagonist luzindole (5 mu g, intraven tricular) did not modulate the DOI effect but antagonized the melatonin (3 mg/kg, i.p.) reversal of 5-HT2A agonist response. The present data suggest that melatonin reversal of DOI-induced hypophagia could be due to suppressi on of 5-HT2A mediated activation of HPA axis. (C) 2000 Elsevier Science B.V . All rights reserved.