Melanocortin mediated inhibition of feeding behavior in rats

Melanocortinergic neurons are believed to play a role in the control of foo d intake. Melanocortin receptor agonists and antagonists modulate feeding i n several mouse models of chemically and genetically induced hyperphagia. T o date, little information is available describing the role of this neurolo gical system in the control of the natural feeding cycle in genetically int act rats. To evaluate the involvement of melanocortins in spontaneous nocturnal feedi ng, the synthetic melanocortin receptor agonist, MTII and the antagonist, S HU9119 were administered ICV (third ventricle) alone and in combination. Do se-dependent inhibition or stimulation of food intake was observed with MTI I or SHU9119, respectively. Go-injections containing equal concentrations o f MTII and SHU9119 resulted in food intake that was indistinguishable from controls. Food intake patterns observed in studies in which various dose co mbinations of MTII and SHU9119 were co-injected are consistent with the con cept that both affect feeding by acting on similar melanocortin receptors, The hypothesis that effects of melanocortins on feeding may be mediated via an NPY related pathway was tested by cc-injecting MTII and NPY in a 2-h sa tiated food intake paradigm. MTII inhibited food intake induced by 5.0 mu g hNPY in a dose dependent manner with the highest dose tested abolishing th e NPY feeding response. The studies suggest that melanocortins act via specific receptors to contro l food intake in rats, possibly via an NPY related pathway. If similar neur ochemical processes operate in humans, selectively modulating specific mela nocortin receptor signaling may be an approach to the treatment of human ob esity.