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, Basel