The Central Effects of Orexin‐A in the Hypothalamic‐Pituitary‐Adrenal Axis In Vivo and In Vitro in Male Rats

Abstract 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.