Orexin-induced food intake involves neuropeptide Y pathway

Orexins (orexin-A and -B) are recently identified neuropeptides, which are thought to be implicated in the regulation of feeding behavior. We used a NPY-Y1 receptor specific antagonist, BIB03304, to examine whether NPY is involved in orexin-induced feeding behavior. Intracerebroventricular administration of orexin-A (10 nmol) induced food intake in rats (food intake for 3 h; vehicle 0.3 +/- 0.2 g vs. orexin-A 10 nmol, 4.0 +/- 0.5 g, n = 4). Orexin-induced feeding behavior was partially inhibited by prior administration of BIB03304 (3 h food intake: orexin-A 10 nmol, 4.0 +/- 0.5 g vs. BIB03304 (60 mu g) + orexin-A 10 nmol, 2.2 +/- 0.2 g, n = 4). A low dose of BIB03304 (30 mu g) did not show a significant inhibitory effect. BIB03457, an inactive enantiomer, used as a negative control, did not show any inhibitory effect on orexin-A-induced feeding behavior. Fos expression was observed in NPY-containing neurons in the arcuate nucleus 1 h after orexin-A (10 nmol) was administered intracerebroventricularly (control 0.3 +/- 0.08%, orexin-A 10.2 +/- 0.8%, n = 5 rats/group). These observations suggest that NPY is involved in orexin-induced feeding behavior. However, BIB03304 did not completely abolish the effect of orexin-A. These results suggest that orexin-A elicits feeding behavior partially via the NPY pathway. The NPY system could be the one of downstream pathways by which orexin-A induces feeding behavior. Another pathway may also be involved in orexin-A-induced feeding behavior, because BIB03304 did not completely abolish orexin-A-induced feeding behavior. (C) 2000 Published by Elsevier Science B.V. All rights reserved.