The Role of Neuropeptide Y in Orexin‐Induced Hypothalamic‐Pituitary‐Adrenal Activation

Abstract

The role of neuropeptide Y (NPY) in the mediation of orexin-induced hypothalamic-pituitary-adrenal (HPA) activation was investigated in the rat. The HPA system was stimulated by intracerebroventricular (i.c.v.) administration of orexin-A or orexin-B (140 or 280 pmol, respectively) and the plasma concentration of corticosterone was used as an index of the degree of activation. i.c.v. pretreatment with NPY antagonist or NPY antiserum (30 min or 24 h before orexin administration, respectively) inhibited the orexin-induced corticosterone release. The inhibitory actions of the antagonist and the antiserum were revealed by the dose-response curve; the highest concentrations practically abolished the HPA activation evoked by the orexins. These data suggest that the HPA system-stimulating effect of the orexins may be mediated by NPY.

International Union of Basic and Clinical Pharmacology. LXXXVI. Orexin Receptor Function, Nomenclature and Pharmacology

“…The authors of the preclinical study suggest that CRF, 5-HT, and NPY may be involved in mediating the anxiogenic effects of OX-A. Indeed, others have substantiated the involvement of these systems in mediating stress-related orexinergic effects by showing a reduction in orexin-mediated stress behaviors by pretreatment with the CRF antagonist ␣-helical CRF (Ida et al, 2000), an altered sleep response to restraint stress in serotonin transporter knockout mice (Rachalski et al, 2009), and an inhibition of orexin-induced activation of the hypothalamicpituitary axis by an NPY antagonist (Já szberényi et al, 2001). investigated the effects of administration of OX-A and OX-B into the paraventricular nucleus of the thalamus, a site characterized by orexincontaining fibers and known to innervate forebrain areas associated with fear and anxiety.…”

Orexins: from neuropeptides to energy homeostasis and sleep/wake regulation

“…A growing number of publications indicate that orexin neuropeptides are also involved in endocrine regulation via the hypothalamo-pituitary axis [2,9,48,49,50]. Regulation of the sympathetic system [64,125], thermogenesis and the hypothalamo-pituitary axis is consistent with orexin's proposed roles in promoting wakefulness and metabolic rate [128].…”

Orexins in the Regulation of the Hypothalamic-Pituitary-Adrenal Axis

“…Accordingly, the orexin-induced surge in the blood level of corticosterone (see section IV.B.2.) was blocked by pretreatment with a NPY antagonist or NPY antiserum (Jaszberényi et al, 2001). However, more recent findings did not confirm the involvement of NPY in the orexin-induced stimulation of HPA axis in rats (Moreno et al, 2005).…”

“…Orexin-A was found to enhance both ACTH and corticosterone blood levels, with the corticosterone response being slightly delayed (Ida et al, 2000;Jaszberényi et al, 2000;Kuru et al, 2000;Al-Barazanji et al, 2001;Russell et al, 2001;Brunton and Russell, 2003). Orexin-B was less effective than orexin-A (Jaszberényi et al, 2000(Jaszberényi et al, , 2001Kuru et al, 2000), thereby suggesting that the effect was mediated by both OX1-Rs and OX2-Rs (see section II.B.). The ACTH and corticosterone responses to orexin-A were blunted in pregnant rats (Brunton and Russell, 2003), a finding not apparently in keeping with the reported enhanced expression of pp-orexin during pregnancy (see section III.A.1.).…”