PMID- 18475271
OWN - NLM
STAT- MEDLINE
DCOM- 20090408
LR  - 20181201
IS  - 1476-5578 (Electronic)
IS  - 1359-4184 (Linking)
VI  - 13
IP  - 11
DP  - 2008 Nov
TI  - Conditional mouse mutants highlight mechanisms of corticotropin-releasing hormone 
      effects on stress-coping behavior.
PG  - 1028-42
LID - 10.1038/mp.2008.51 [doi]
AB  - 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.
FAU - Lu, A
AU  - Lu A
AD  - Max Planck Institute of Psychiatry, Munich, Germany.
FAU - Steiner, M A
AU  - Steiner MA
FAU - Whittle, N
AU  - Whittle N
FAU - Vogl, A M
AU  - Vogl AM
FAU - Walser, S M
AU  - Walser SM
FAU - Ableitner, M
AU  - Ableitner M
FAU - Refojo, D
AU  - Refojo D
FAU - Ekker, M
AU  - Ekker M
FAU - Rubenstein, J L
AU  - Rubenstein JL
FAU - Stalla, G K
AU  - Stalla GK
FAU - Singewald, N
AU  - Singewald N
FAU - Holsboer, F
AU  - Holsboer F
FAU - Wotjak, C T
AU  - Wotjak CT
FAU - Wurst, W
AU  - Wurst W
FAU - Deussing, J M
AU  - Deussing JM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080513
PL  - England
TA  - Mol Psychiatry
JT  - Molecular psychiatry
JID - 9607835
RN  - 0 (DMP 696)
RN  - 0 (Gt(ROSA)26Sor non-coding RNA, mouse)
RN  - 0 (Intermediate Filament Proteins)
RN  - 0 (Methyltyrosines)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Nes protein, mouse)
RN  - 0 (Nestin)
RN  - 0 (Proteins)
RN  - 0 (Pyrazoles)
RN  - 0 (RNA, Untranslated)
RN  - 0 (Receptors, Corticotropin-Releasing Hormone)
RN  - 0 (Triazines)
RN  - 23434-96-0 (4-chlorophenylalanine methyl ester)
RN  - 4502-13-0 (alpha-methyltyrosine methyl ester)
RN  - 5CLY6W2H1M (CRF receptor type 1)
RN  - 9015-71-8 (Corticotropin-Releasing Hormone)
RN  - R5J7E3L9SP (Fenclonine)
SB  - IM
MH  - Adaptation, Psychological/drug effects/physiology
MH  - Analysis of Variance
MH  - Animals
MH  - Brain Chemistry/drug effects
MH  - Central Nervous System/anatomy & histology/drug effects/*metabolism
MH  - Corticotropin-Releasing Hormone/antagonists & inhibitors/*genetics/*metabolism
MH  - Exploratory Behavior
MH  - Female
MH  - Fenclonine/administration & dosage/analogs & derivatives
MH  - Hindlimb Suspension
MH  - Hypothalamo-Hypophyseal System/drug effects/metabolism
MH  - Intermediate Filament Proteins/genetics
MH  - Male
MH  - Methyltyrosines/administration & dosage
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Mutant Strains
MH  - Mice, Transgenic
MH  - Nerve Tissue Proteins/genetics
MH  - Nestin
MH  - Pituitary-Adrenal System/drug effects/metabolism
MH  - Proteins/genetics
MH  - Pyrazoles/pharmacology
MH  - RNA, Untranslated
MH  - Radioimmunoassay/methods
MH  - Receptors, Corticotropin-Releasing Hormone/genetics/metabolism
MH  - Stress, Physiological/*genetics
MH  - Stress, Psychological/drug therapy/etiology/*genetics
MH  - Swimming
MH  - Triazines/pharmacology
EDAT- 2008/05/14 09:00
MHDA- 2009/04/09 09:00
CRDT- 2008/05/14 09:00
PHST- 2008/05/14 09:00 [pubmed]
PHST- 2009/04/09 09:00 [medline]
PHST- 2008/05/14 09:00 [entrez]
AID - mp200851 [pii]
AID - 10.1038/mp.2008.51 [doi]
PST - ppublish
SO  - Mol Psychiatry. 2008 Nov;13(11):1028-42. doi: 10.1038/mp.2008.51. Epub 2008 May 
      13.