LACK OF NPY-INDUCED FEEDING IN COBALT PROTOPORPHYRIN-TREATED RATS IS A POSTRECEPTOR DEFECT

The administration of cobalt protoporphyrin results in transient decre ases in food intake and prolonged weight loss in rats. After IVC injec tion of cobalt protoporphyrin, the food intake of treated rats falls t o 10% of vehicle-treated control rats within 48 h. At the same time, t he concentrations of mRNA for neuropeptide Y increase approximately tw ofold in the hypothalamus. The failure of these animals to display a f eeding response to elevation of endogenous NPY concentration is mimick ed by their failure to respond to exogenous, ICV injections of neurope ptide Y. Because NPY binding studies are confounded by high nonspecifi c binding, radiolabeled PYY was used to measure binding to hypothalami c membranes and for autoradiography with hypothalamic sections. No abn ormalities in the number of receptors or the affinity of the binding i nteraction were noted. In addition, hypothalamic concentrations of cyc lic AMP were unchanged following treatment with either cobalt protopor phyrin or NPY. These results indicate that the locus of the failure of CoPP-treated animals to feed after administration of NPY must be eith er distal to, or unrelated to, the NPY receptor in the hypothalamus.