The central effects of orexin-A in the hypothalamic-pituitary-adrenal axis in vivo and in vitro in male rats

J Neuroendocrinol. 2001 Jun;13(6):561-6. doi: 10.1046/j.1365-2826.2001.00672.x.


Orexin-A is synthesized in the posterolateral hypothalamus and immunoreactive fibres project to many central nervous system structures, including the paraventricular nucleus, which is rich in corticotropin releasing factor (CRF) neurones and neuropeptide Y (NPY) innervation. We investigated the central effects of orexin-A on the hypothalamic-pituitary-adrenal (HPA) axis by measuring plasma concentrations of corticosterone and adrenocorticotropic hormone (ACTH) in vivo. We explored the potential neuropeptide pathways involved by investigating the effects of orexin-A on CRF, NPY, arginine vasopressin (AVP) and noradrenaline release from hypothalamic explants in vitro. Intracerebroventricular (i.c.v.) injection of orexin-A (3 nmol) in male rats stimulated increases in plasma concentrations of corticosterone between 10 and 40 min after injection, and of plasma ACTH at 20 and 90 min after injection. Orexin-A significantly stimulated CRF and NPY release from hypothalamic explants in vitro. Orexin-A did not stimulate CRF release in the presence of the selective NPY Y1 receptor antagonist, BIBP3226. BIBP3226 alone did not alter CRF release from hypothalamic explants. Orexin-A had no effect in vitro on the release of other neuropeptides, AVP and noradrenaline, involved in the central regulation of the HPA axis. These results suggest that orexin-A is involved in activation of the HPA axis, and that these effects could be mediated via the release of NPY.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Glands / drug effects*
  • Adrenocorticotropic Hormone / blood
  • Animals
  • Arginine / analogs & derivatives*
  • Arginine / pharmacology
  • Arginine Vasopressin / metabolism
  • Carrier Proteins / administration & dosage
  • Carrier Proteins / pharmacology*
  • Corticosterone / blood
  • Corticotropin-Releasing Hormone / metabolism
  • Culture Techniques
  • Hypothalamus / drug effects*
  • Hypothalamus / metabolism
  • Injections, Intraventricular
  • Intracellular Signaling Peptides and Proteins*
  • Kinetics
  • Male
  • Neuropeptide Y / metabolism
  • Neuropeptides / administration & dosage
  • Neuropeptides / pharmacology*
  • Norepinephrine / metabolism
  • Orexins
  • Pituitary Gland / drug effects*
  • Rats
  • Rats, Wistar


  • BIBP 3226
  • Carrier Proteins
  • Intracellular Signaling Peptides and Proteins
  • Neuropeptide Y
  • Neuropeptides
  • Orexins
  • Arginine Vasopressin
  • Adrenocorticotropic Hormone
  • Corticotropin-Releasing Hormone
  • Arginine
  • Corticosterone
  • Norepinephrine