Evidence that NPYY1 receptors are involved in stimulation of feeding by orexins (hypocretins) in sated rats

Neuropeptide Y (NPY) produced in the arcuate nucleus (ARC) of the hypothala mus stimulates feeding both directly by activating NPY receptors and indire ctly through release of the orexigenic peptides, galanin and beta-endorphin (beta-END), in the paraventricular nucleus (PVN) and surrounding neural si tes. Orexin A and orexin B, produced outside the ARC in the lateral hypotha lamic area (LH), have recently been shown to stimulate feeding. In the pres ent studies we tested the hypothesis that NPYergic signaling may mediate fe eding stimulated by orexins. In adult male rats injected intracerebroventri cularly (icv) with orexin A (3, 10, 15 nmol) or orexin B (3, 10, 30 nmol) f eeding was stimulated in a dose-dependent manner; maximal feeding was seen after 15 nmol orexin A and 30 nmol orexin B. To determine whether NPY may m ediate this orexin stimulated feeding, we used 1229U91, a selective NPY Y1 receptor antagonist (NPY-A). Whereas NPY-A on its own was ineffective, it s uppressed NPY-induced feeding. Furthermore, NPY-A completely blocked the fe eding evoked by either orexin A (15 nmol) or orexin B (30 nmol), These resu lts show that orexin A and B stimulate feeding and further suggest that the se excitatory effects may be mediated by NPYergic signaling through Y1 rece ptors. These findings are in accord with the view that the orexin-NPY pathw ay may comprise a functional link upstream from NPY within the hypothalamic appetite regulating network. (C) 2000 Elsevier Science B.V. All rights res erved.