Orexin-induced food intake involves neuropeptide Y pathway

Brain Res. 2000 Mar 24;859(2):404-9. doi: 10.1016/s0006-8993(00)02043-6.


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, BIBO3304, 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 BIBO3304 (3 h food intake: orexin-A 10 nmol, 4.0+/-0.5 g vs. BIBO3304 (60 microgram) + orexin-A 10 nmol, 2.2+/-0.2 g, n=4). A low dose of BIBO3304 (30 microgram) did not show a significant inhibitory effect. BIBO3457, 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, BIBO3304 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 BIBO3304 did not completely abolish orexin-A-induced feeding behavior.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arginine / analogs & derivatives
  • Arginine / pharmacology
  • Carrier Proteins / metabolism*
  • Carrier Proteins / pharmacology*
  • Eating / drug effects*
  • Eating / physiology*
  • Hypothalamus / cytology
  • Hypothalamus / drug effects*
  • Hypothalamus / metabolism*
  • Intracellular Signaling Peptides and Proteins*
  • Male
  • Neural Pathways / cytology
  • Neural Pathways / drug effects*
  • Neural Pathways / metabolism*
  • Neuropeptide Y / drug effects*
  • Neuropeptide Y / metabolism*
  • Neuropeptides / metabolism*
  • Neuropeptides / pharmacology*
  • Orexin Receptors
  • Orexins
  • Rats
  • Rats, Wistar
  • Receptors, G-Protein-Coupled
  • Receptors, Neuropeptide
  • Receptors, Neuropeptide Y / antagonists & inhibitors*
  • Receptors, Neuropeptide Y / metabolism*


  • Carrier Proteins
  • Intracellular Signaling Peptides and Proteins
  • Neuropeptide Y
  • Neuropeptides
  • Orexin Receptors
  • Orexins
  • Receptors, G-Protein-Coupled
  • Receptors, Neuropeptide
  • Receptors, Neuropeptide Y
  • Arginine
  • BIBO 3304