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Conditional mouse mutants highlight mechanisms of corticotropin-releasing hormone effects on stress-coping behavior.
Mol. Psychiatry 13, 1028-1042 (2008)
Hypersecretion of central corticotropin-releasing hormone (CRH) has been implicated in the pathophysiology of affective disorders. Both, basic and clinical studies suggested that disrupting CRH signaling through CRH type 1 receptors (CRH-R1) can ameliorate stress-related clinical conditions. To study the effects of CRH-R1 blockade upon CRH-elicited behavioral and neurochemical changes we created different mouse lines overexpressing CRH in distinct spatially restricted patterns. CRH overexpression in the entire central nervous system, but not when overexpressed in specific forebrain regions, resulted in stress-induced hypersecretion of stress hormones and increased active stress-coping behavior reflected by reduced immobility in the forced swim test and tail suspension test. These changes were related to acute effects of overexpressed CRH as they were normalized by CRH-R1 antagonist treatment and recapitulated the effect of stress-induced activation of the endogenous CRH system. Moreover, we identified enhanced noradrenergic activity as potential molecular mechanism underlying increased active stress-coping behavior observed in these animals. Thus, these transgenic mouse lines may serve as animal models for stress-elicited pathologies and treatments that target the central CRH system.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
corticotropin-releasing hormone; depression; forced swim test; HPA axis; ROSA26; DMP696
Language
Publication Year
2008
HGF-reported in Year
2008
ISSN (print) / ISBN
1359-4184
e-ISSN
1476-5578
Journal
Molecular Psychiatry
Quellenangaben
Volume: 13,
Issue: 11,
Pages: 1028-1042
Publisher
Nature Publishing Group
Reviewing status
Peer reviewed
Institute(s)
Institute of Developmental Genetics (IDG)
POF-Topic(s)
30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
Research field(s)
Genetics and Epidemiology
PSP Element(s)
G-520600-001
Scopus ID
54249128702
Erfassungsdatum
2008-12-31