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  Conditional mouse mutants highlight mechanisms of corticotropin-releasing hormone effects on stress-coping behavior

Lu, A., Steiner, M. A., Whittle, N., Vogl, A. M., Walser, S. M., Ableitner, M., et al. (2008). Conditional mouse mutants highlight mechanisms of corticotropin-releasing hormone effects on stress-coping behavior. Molecular Psychiatry, 13(11), 1028-1042.

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Genre: Journal Article
Alternative Title : Mol. Psychiatr.

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 Creators:
Lu, A.1, Author           
Steiner, M. A.2, Author           
Whittle, N., Author
Vogl, A. M.3, Author           
Walser, S. M.3, Author           
Ableitner, M.3, Author           
Refojo, D.3, Author           
Ekker, M., Author
Rubenstein, J. L., Author
Stalla, G. K.4, Author
Singewald, N., Author
Holsboer, F.5, Author           
Wotjak, C. T.2, Author           
Wurst, W.4, Author           
Deussing, J. M.3, Author           
Affiliations:
1AG Almeida, Osborne, Florian Holsboer (Direktor), Max Planck Institute of Psychiatry, Max Planck Society, ou_1607141              
2AG Wotjak, Carsten, Florian Holsboer (Direktor), Max Planck Institute of Psychiatry, Max Planck Society, ou_1607166              
3AG Deussing, Jan, Florian Holsboer (Direktor), Max Planck Institute of Psychiatry, Max Planck Society, ou_1607145              
4Max Planck Institute of Psychiatry, Max Planck Society, ou_1607137              
5Florian Holsboer (Direktor), Max Planck Institute of Psychiatry, Max Planck Society, ou_1607139              

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Free keywords: corticotropin-releasing hormone; depression; forced swim test; HPA axis; ROSA26; DMP696
 Abstract: 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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Language(s): eng - English
 Dates: 2008-11
 Publication Status: Issued
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: eDoc: 395628
ISI: 000260632200006
 Degree: -

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Title: Molecular Psychiatry
  Alternative Title : Mol. Psychiatr.
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: -
Pages: - Volume / Issue: 13 (11) Sequence Number: - Start / End Page: 1028 - 1042 Identifier: ISSN: 1359-4184