Lack of NPY-induced feeding in cobalt protoporphyrin-treated rats is a postreceptor defect

The administration of cobalt protoporphyrin results in transient decreases in food intake and prolonged weight loss in rats. After IVC injection of cobalt protoporphyrin, the food intake of treated rats falls to 10% of vehicle-treated control rats within 48 h. At the same time, the concentrations of mRNA for neuropeptide Y increase approximately twofold in the hypothalamus. The failure of these animals to display a feedings response to elevation of endogenous NPY concentration is mimicked by their failure to respond to exogenous. ICV injections of neuropeptide Y. Because NPY binding studies are confounded by high nonspecific binding, radiolabeled PYY was used to measure binding to hypothalamic membranes and for autoradiography with hypothalamic sections. No abnormalities in the number of receptors or the affinity of the binding interaction were noted. In addition, hypothalamic concentrations of cyclic AMP were unchanged following treatment with either cobalt protoporphyrin or NPY. These results indicate that the locus of the failure of CoPP-treated animals to feed after administration of NPY must be either distal to, or unrelated to, the NPY receptor in the hypothalamus.