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

MPG-Autoren
http://pubman.mpdl.mpg.de/cone/persons/resource/persons80425

Lu,  A.
AG Almeida, Osborne, Florian Holsboer (Direktor), Max Planck Institute of Psychiatry, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons80543

Steiner,  M. A.
AG Wotjak, Carsten, Florian Holsboer (Direktor), Max Planck Institute of Psychiatry, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons80568

Vogl,  A. M.
AG Deussing, Jan, Florian Holsboer (Direktor), Max Planck Institute of Psychiatry, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons80574

Walser,  S. M.
AG Deussing, Jan, Florian Holsboer (Direktor), Max Planck Institute of Psychiatry, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons80244

Ableitner,  M.
AG Deussing, Jan, Florian Holsboer (Direktor), Max Planck Institute of Psychiatry, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons80487

Refojo,  D.
AG Deussing, Jan, Florian Holsboer (Direktor), Max Planck Institute of Psychiatry, Max Planck Society;

Stalla,  G. K.
Max Planck Institute of Psychiatry, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons80372

Holsboer,  F.
Florian Holsboer (Direktor), Max Planck Institute of Psychiatry, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons80598

Wotjak,  C. T.
AG Wotjak, Carsten, Florian Holsboer (Direktor), Max Planck Institute of Psychiatry, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons80599

Wurst,  W.
Max Planck Institute of Psychiatry, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons80301

Deussing,  J. M.
AG Deussing, Jan, Florian Holsboer (Direktor), Max Planck Institute of Psychiatry, Max Planck Society;

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Zitation

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.


Zitierlink: http://hdl.handle.net/11858/00-001M-0000-000E-939D-F
Zusammenfassung
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.