Control of stress-induced acth secretion by vasopressin and crh: additional evidence

Vasopressin and CRH have complementary roles in the secretion of ACTH following different stress modalities. The concomitant use of V-1b and CRF1 receptor antagonists completely inhibits ACTH secretion in response to different stress modalities. The combination of the CRF1 antagonist SSR125543 with the V-1b antagonist SSR149415 effectively suppressed plasma ACTH 1.30 h after injection in rats stressed by ether vapor inhalation for 1 min, restraint stress for 1 h or forced swimming for 5 min. The duration of the effect was also studied. The CRF1 antagonist effectively suppressed ACTH secretion in restraint stress, while the V-1b antagonist was effective against ether inhalation. Both antagonists were necessary to block the forced swimming stress response. SSR125543 induced a prolonged effect and can be used in a model of prolonged HPA axis blockade. (C) 2016 S. Karger AG, BaselAFIPFAPESP [98/14303-3, 04/12871-7, 15/08098-5, 2013/18897-7]CAPESFundacao ButantanDepartment of Psychobiology, Universidade Federal de São Paulo (UNIFESP)Laboratory of Pharmacology, Instituto ButantanLaboratory of Molecular Neuropharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, BrazilDepartment of Psychobiology, Universidade Federal de São Paulo (UNIFESP)Sanofi-Aventis: SSR125543Sanofi-Aventis: SSR149415FAPESP: 98/14303-3FAPESP: 04/12871-7FAPESP: 15/08098-5FAPESP: 2013/18897-7Web of Scienc