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Refojo, D.* ; Schweizer, M.* ; Kuehne, C.* ; Ehrenberg, S.* ; Thoeringer, C.* ; Vogl, A.M.* ; Dedic, N.* ; Schumacher, M.* ; von Wolff, G.* ; Avrabos, C.* ; Touma, C.* ; Engblom, D.* ; Schütz, G.* ; Nave, K.A.* ; Eder, M.* ; Wotjak, C.T.* ; Sillaber, I.* ; Holsboer, F.* ; Wurst, W. ; Deussing, J.M.*

Glutamatergic and dopaminergic neurons mediate anxiogenic and anxiolytic effects of CRHR1.

Science 333, 1903-1907 (2011)
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The corticotropin-releasing hormone receptor 1 (CRHR1) critically controls behavioral adaptation to stress and is causally linked to emotional disorders. Using neurochemical and genetic tools, we determined that CRHR1 is expressed in forebrain glutamatergic and γ-aminobutyric acid-containing (GABAergic) neurons as well as in midbrain dopaminergic neurons. Via specific CRHR1 deletions in glutamatergic, GABAergic, dopaminergic, and serotonergic cells, we found that the lack of CRHR1 in forebrain glutamatergic circuits reduces anxiety and impairs neurotransmission in the amygdala and hippocampus. Selective deletion of CRHR1 in midbrain dopaminergic neurons increases anxiety-like behavior and reduces dopamine release in the prefrontal cortex. These results define a bidirectional model for the role of CRHR1 in anxiety and suggest that an imbalance between CRHR1-controlled anxiogenic glutamatergic and anxiolytic dopaminergic systems might lead to emotional disorders.
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Publication type Article: Journal article
Document type Scientific Article
Keywords no keywords
Language english
Publication Year 2011
HGF-reported in Year 2011
ISSN (print) / ISBN 0036-8075
e-ISSN 1095-9203
Journal Science
Quellenangaben Volume: 333, Issue: 6051, Pages: 1903-1907 Article Number: , Supplement: ,
Publisher American Association for the Advancement of Science (AAAS)
Reviewing status Peer reviewed
Institute(s) Institute of Developmental Genetics (IDG)
POF-Topic(s) 30204 - Cell Programming and Repair
30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
Research field(s) Genetics and Epidemiology
PSP Element(s) G-500500-001
G-520600-001
DOI 10.1126/science.1202107
Scopus ID 80053365601
PubMed ID 21885734
Erfassungsdatum 2011-12-01
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