Publication Date:
2011-09-03
Description:
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 gamma-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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Refojo, Damian -- Schweizer, Martin -- Kuehne, Claudia -- Ehrenberg, Stefanie -- Thoeringer, Christoph -- Vogl, Annette M -- Dedic, Nina -- Schumacher, Marion -- von Wolff, Gregor -- Avrabos, Charilaos -- Touma, Chadi -- Engblom, David -- Schutz, Gunther -- Nave, Klaus-Armin -- Eder, Matthias -- Wotjak, Carsten T -- Sillaber, Inge -- Holsboer, Florian -- Wurst, Wolfgang -- Deussing, Jan M -- New York, N.Y. -- Science. 2011 Sep 30;333(6051):1903-7. doi: 10.1126/science.1202107. Epub 2011 Sep 1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Max Planck Institute of Psychiatry, Munich, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21885734" target="_blank"〉PubMed〈/a〉
Keywords:
Amygdala/metabolism
;
Animals
;
*Anxiety
;
Behavior, Animal
;
Corticotropin-Releasing Hormone/metabolism
;
Dopamine/*metabolism
;
Fear
;
Glutamic Acid/*metabolism
;
Hippocampus/metabolism
;
Male
;
Memory
;
Mesencephalon
;
Mice
;
Mice, Knockout
;
Motor Activity
;
Neurons/*metabolism
;
Prefrontal Cortex/metabolism
;
Prosencephalon/cytology/metabolism
;
Receptors, Corticotropin-Releasing Hormone/antagonists &
;
inhibitors/genetics/*metabolism
;
Synaptic Transmission
;
Ventral Tegmental Area/metabolism
;
gamma-Aminobutyric Acid/metabolism
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
Permalink
