Evidence of NPY Y5 receptor involvement in food intake elicited by orexin A in sated rats

Intracerebroventricular (icv) injections of orexin A stimulate feeding in sated rats. Since neuropeptide Y is a potent orexigenic peptide and orexin-containing neurons are morphologically linked with NPY-producing neurons in the hypothalamus, we evaluated the functional relationship between the two orexigenic peptides. The results show that whereas it was ineffective on its own, a selective NPY Y5 receptor antagonist, injected icv 15 min. before orexin A significantly suppressed orexin A-induced feeding. Since previous investigations demonstrated that an NPY Y1 receptor antagonist also inhibits feeding induced by orexin A, the current results further underscore the existence of a functional link between orexin and NPY producing neurons as the orexin network appears to be capable of influencing NPYergic signaling through Y1 and Y5 receptors to stimulate feeding.