Effects of orexins on the hypothalamic-pituitary-adrenal system

The effects of the recently identified neuropeptides orexin-A and orexin-B on the hypothalamic-pituitary-adrenal (HPA) system were investigated. An in vivo system was used to assess the central effects of both orexin-A and or exin-B. Different doses of the orexins (2.8-560 pmol) were administered int racerebroventricularly (i.c.v.) to adult male rats, and plasma corticostero ne was used as an index of the degree of the activation of the HPA system. Both peptides exhibited a clear dose-response action, although orexin-B pro ved to be less effective than orexin-A. Pretreatment with the corticotropin -releasing hormone (CRH) antagonist alpha -helical CRH9-41 completely preve nted the action of the orexins. Orexin-A, orexin-B or adrenocorticotropic h ormone (ACTH) was further administered intraperitoneally (i.p.). While ACTH evoked a significant adrenal response, the orexins did not influence the b asal secretion. Adrenal slices, oxygenized and perifused with Krebs' soluti on, were also treated with orexin-A, orexin-B or ACTH. Both orexins failed to modify the release of corticosterone, but ACTH induced a marked adrenal response. This study suggests that these appetite-regulating peptides might activate the HPA system at a central level but neither orexin-A nor orexin -B appears to modulate directly the adrenal corticosterone release.