Glutamatergic and Dopaminergic Neurons Mediate Anxiogenic and Anxiolytic Effects of CRHR1

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.

Schweizer, MartinMax Planck Inst Psychiat, Munich, Germany (författare)
Kuehne, ClaudiaMax Planck Inst Psychiat, Munich, Germany (författare)
Ehrenberg, StefanieMax Planck Inst Psychiat, Munich, Germany (författare)
Thoeringer, ChristophMax Planck Inst Psychiat, Munich, Germany (författare)
Vogl, Annette MMax Planck Inst Psychiat, Munich, Germany (författare)
Dedic, NinaMax Planck Inst Psychiat, Munich, Germany (författare)
Schumacher, MarionMax Planck Inst Psychiat, Munich, Germany (författare)
von Wolff, GregorMax Planck Inst Psychiat, Munich, Germany (författare)
Avrabos, CharilaosMax Planck Inst Psychiat, Munich, Germany (författare)
Touma, ChadiMax Planck Inst Psychiat, Munich, Germany (författare)
Engblom, DavidGerman Canc Res Ctr, Heidelberg, Germany(Swepub:liu)daven69 (författare)
Schuetz, GuentherGerman Canc Res Ctr, Heidelberg, Germany (författare)
Nave, Klaus-ArminMax Planck Inst Expt Med, Gottingen, Germany (författare)
Eder, MatthiasMax Planck Inst Psychiat, Munich, Germany (författare)
Wotjak, Carsten TMax Planck Inst Psychiat, Munich, Germany (författare)
Sillaber, IngeMax Planck Inst Psychiat, Munich, Germany (författare)
Holsboer, FlorianMax Planck Inst Psychiat, Munich, Germany (författare)
Wurst, WolfgangMax Planck Inst Psychiat, Munich, Germany (författare)
Deussing, Jan MMax Planck Inst Psychiat, Munich, Germany (författare)
Max Planck Inst Psychiat, Munich, GermanyGerman Canc Res Ctr, Heidelberg, Germany (creator_code:org_t)

Ingår i:Science: American Association for the Advancement of Science (AAAS)333:6051, s. 1903-19070036-80751095-9203

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