Stress-induced behaviors require the corticotropin-releasing hormone (CRH)receptor, but not CRH

Corticotropin-releasing hormone (CRH) is a central regulator of the hormona l stress response, causing stimulation of corticotropin and glucocorticoid secretion. CRH is also widely believed to mediate stress-induced behaviors, implying a broader, integrative role for the hormone in the psychological stress response. Mice lacking the CRH gene exhibit normal stress-induced be havior that is specifically blocked by a CRH type 1 receptor antagonist. Th e other known mammalian ligand for CRH receptors is urocortin, Normal and C RH-deficient mice have an identical distribution of urocortin mRNA, which i s confined to the region of the Edinger-Westphal nucleus, and is absent fro m regions known to mediate stress-related behaviors. Since the Edinger-West phal nucleus is not known to project to any brain regions believed to play a role in anxiety-like behavior, an entirely different pathway must be post ulated for urocortin in the Edinger-Westphal nucleus to mediate these behav iors in CRH-deficient mice. Alternatively, an unidentified CRH-like molecul e other than CRH or urocortin, acting through the CRH receptors in brain re gions believed to mediate stress-induced behaviors, may mediate the behavio ral response to stress, either alone or in concert with CRH.