Stress-Induced Behaviors Require the Corticotropin-Releasing Hormone (CRH) Receptor, but Not CRH

• Published in: Proceedings of the National Academy of Sciences - PNAS 1999-07, Vol.96 (14), p.8283-8288
• Main Authors: Weninger, Stacie C., Dunn, Adrian J., Muglia, Louis J., Dikkes, Pieter, Miczek, Klaus A., Swiergiel, Artur H., Berridge, Craig W., Majzoub, Joseph A.
• Format: Article
• Language: English
• Subjects: Amygdala; Animal behavior; Animals; Avoidance Learning - physiology; Biological Sciences; Cerebral Ventricles - physiology; Conditioning, Operant - physiology; Corticotropin-Releasing Hormone - administration & dosage; Corticotropin-Releasing Hormone - deficiency; Corticotropin-Releasing Hormone - genetics; Corticotropin-Releasing Hormone - physiology; Crosses, Genetic; Electroshock; Fear; Female; Freezing; Gene Expression Regulation; Genes; Genotypes; Hormones; Hybrid vehicles; In situ hybridization; Injections, Intraventricular; Learning - physiology; Male; Messenger RNA; Mice; Mice, Inbred C57BL; Mice, Inbred Strains; Mice, Knockout; Motor Activity - physiology; Pain - genetics; Pain - physiopathology; Psychology; Pyrimidines - pharmacology; Pyrroles - pharmacology; Receptors; Receptors, Corticotropin-Releasing Hormone - antagonists & inhibitors; Receptors, Corticotropin-Releasing Hormone - physiology; Regional identity; Reinforcement (Psychology); Stress; Stress, Psychological; Transcription, Genetic; Urocortins
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.96.14.8283

Corticotropin-releasing hormone (CRH) is a central regulator of the hormonal 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 behavior that is specifically blocked by a CRH type 1 receptor antagonist. The other known mammalian ligand for CRH receptors is urocortin. Normal and CRH-deficient mice have an identical distribution of urocortin mRNA, which is confined to the region of the Edinger-Westphal nucleus, and is absent from regions known to mediate stress-related behaviors. Since the Edinger-Westphal 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 postulated for urocortin in the Edinger-Westphal nucleus to mediate these behaviors in CRH-deficient mice. Alternatively, an unidentified CRH-like molecule other than CRH or urocortin, acting through the CRH receptors in brain regions believed to mediate stress-induced behaviors, may mediate the behavioral response to stress, either alone or in concert with CRH.