Central melanocortin receptors mediate changes in food intake in the rhesus macaque

In rodents, stimulation of melanocortin-3 and -4 receptor subtypes (MC3-R a nd MC4-R) causes a reduction in food intake, whereas antagonism of MC3-R an d MC4-R increases food intake. This report describes the effects of the sta ble (alpha MSH analog, NDP-MSH ([Nle(4), D-Phe(7)]alpha MSH), and the endog enous alpha MSH receptor antagonist, ag outi-related protein, on feeding be havior in adult male rhesus macaques. Infusion of NDP-MSH into the lateral cerebral ventricle dose dependently suppressed intake of a normally schedul ed meal without affecting nonfeeding behaviors. Conversely, infusion of ago uti-related protein stimulated food intake during the scheduled afternoon m eal. In addition to these physiological experiments, the effect of fasting on hypothalamic POMC gene expression was assessed by in situ hybridization. Missing a single meal or fasting for 48 h caused a similar reduction in PO MC gene expression in the arcuate nucleus. These results demonstrate that i n the primate, central melanocortin receptors can acutely regulate food int ake and suggest that the central melanocortinergic system is a physiologica l regulator of energy balance in primate species.