Abstract
Vasopressin and CRH have complementary roles in the secretion of ACTH following different stress modalities. The concomitant use of V<sub>1b</sub> and CRF<sub>1</sub> receptor antagonists completely inhibits ACTH secretion in response to different stress modalities. The combination of the CRF<sub>1</sub> antagonist SSR125543 with the V<sub>1b</sub> 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 CRF<sub>1</sub> antagonist effectively suppressed ACTH secretion in restraint stress, while the V<sub>1b</sub> 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.
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