Melanocortin receptor agonist transiently increases oxygen consumption in rats

Acute injections of melanocortin (MC) agonist and antagonist are highly eff ective in reducing or increasing food take, respectively. Much less is know n about how injection of MC receptor active substances affects metabolism, in particular during long term administration. Here we investigated the eff ect of 8 days continuous i.c.v. infusion of either MC receptor agonist MTII or the selective MC4 receptor antagonist HS024 on oxygen consumption, food intake and body weight in rats. We observed significant increase in oxygen consumption 2 days after the start of the MTII infusion. However, this inc rease had disappeared by day 4 of the study. No difference was observed in the oxygen consumption after injection of HS024. MTII substantially decreas ed the food intake during the first days, but then the feeding recovered an d the body weight stabilised at a new level. The immediate effect of the MC receptor agonist on both food intake and metabolism was thus transient, ev en though the weight loss was maintained. The HS024 treated rats were hyper phagic throughout the test period, continuously gaining weight, resulting i n increased fat pads and high leptin levels. This is the first study that d escribes long term effects of MC receptor agonist and antagonist on metabol ism and energy balance. NeuroReport 12:3703-3708 (C) 2001 Lippincott Willia ms & Wilkins.