Central orexin-A activates hypothalamic-pituitary-adrenal axis and stimulates hypothalamic corticotropin releasing factor and arginine vasopressin neurones in conscious rats

The effects of centrally injected orexin-A on plasma adrenocorticotropin (A CTH) and corticosterone levels and corticotropin releasing factor (CRF) aci d arginine vasopressin (AVP) mRNA in the parvocellular cells of the paraven tricular nucleus (PVN) of the rat were investigated, In animals implanted p reviously with a lateral brain ventricle and femoral artery cannula, a sing le i.c.v. injection of orexin-A (10 mug/rat) resulted in a rapid, significa nt increase in plasma ACTH and corticosterone concentrations. Plasma ACTH r eached a peak (12.5-fold greater than basal levels) at 30 min. which was ma intained over 120 min before declining towards control levels by 240 min, P lasma corticosterone concentrations reached a peak (6.7-fold greater than b asal levels) at 30 min. Orexin-A at a higher dose (30 mug/rat) also produce d a rapid increase in plasma ACTH and corticosterone concentrations. The ar ea under the curve for plasma levels of ACTH was similar for both doses of orexin-A, In a second study, orexin-A (10 mug/rat) was injected i.c.v. and brains and pituitaries were rapidly removed after 240 min. In situ hybridiz ation histochemistry revealed that CRF and AVP mRNA levels were significant ly increased in the parvocellular cells of the PVN, Pro-opiomelanocortin mR NA levels in the pituitary gland were not significantly elevated in respons e to orexin-A. These results suggest that orexin-A is able to act centrally to activate the hypothalamic-pituitary-adrenal axis involving stimulation of both CRF and AVP expression.