Reciprocal Interaction between Hypothalamic Orexin‐A and Corticotropin‐releasing Factor under Stressed Condition

Abstract

In response to stressful stimuli, expression of orexin‐A (OXA) is increased within central nervous system. The orexinergic cells reside in lateral hypothalamic area (LHA) have dense projections on hypothalamic paraventricular nucleus (PVN), furthermore, corticotropin‐releasing factor (CRF) receptors are expressed in orexin‐producing neurons within LHA. However, the interaction between these neuropeptides is understood incompletely. Using acute restraint stress (ARS) model in rats, the purpose of the present study was designed to investigate (i) the interaction between hypothalamic OXA and CRF, and (ii) the contribution hypothalamic OXA in CRF‐mediated glucocorticoid release. Adult male Wistar rats underwent stereotaxic cannulation for intracerebroventricular (icv) drug injection and microdialysis 7 days prior to the experiments. Under basal and stressed conditions, microdialysis samples were collected from LHA and PVN to monitor the alterations in OXA and CRF, respectively, whereas, their antagonists were administered centrally prior to the stress loading. The immunoreactivities for both neuropeptides were detected in hypothalamic sections by immunohistochemistry. The corticosterone (CORT) concentrations in plasma samples were assayed using enzyme immunoassay. Compared to their basal levels, OXA and CRF concentrations in microdialysates were increased in ARS‐loaded rats, while they were attenuated significantly by the receptor antagonists. ARS increased the immunoreactivities for OXA and CRF in hypothalamus remarkably, while increasing the plasma CORT. Central preadministration of the antagonists reduced the ARS‐induced increased hypothalamic immunoreactivites and plasma CORT. Under stressed condition, OXA and CRF seem to play in a synergistic signaling pathway through their specific receptors. The endogenous hypothalamic OXA appears to contribute to the CRF‐mediated neuroendocrine stress response. The interaction between OXA and CRF may lead to better understanding of the etiopathogenesis of stress‐related disorders.Support or Funding InformationThe present study was supported by the Research Foundation of Akdeniz University (Project number: TSA‐2017‐2418)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.