title: Glutamatergic and dopaminergic neurons mediate anxiogenic and anxiolytic effects of CRHR1.
abstract: 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.
authors: Max Planck Institute of Psychiatry, Munich, Germany.
authors: Damian
authors: D
authors: Refojo
authors: Martin
authors: M
authors: Schweizer
authors: Claudia
authors: C
authors: Kuehne
authors: Stefanie
authors: S
authors: Ehrenberg
authors: Christoph
authors: C
authors: Thoeringer
authors: Annette M
authors: AM
authors: Vogl
authors: Nina
authors: N
authors: Dedic
authors: Marion
authors: M
authors: Schumacher
authors: Gregor
authors: G
authors: von Wolff
authors: Charilaos
authors: C
authors: Avrabos
authors: Chadi
authors: C
authors: Touma
authors: David
authors: D
authors: Engblom
authors: Günther
authors: G
authors: Schütz
authors: Klaus-Armin
authors: KA
authors: Nave
authors: Matthias
authors: M
authors: Eder
authors: Carsten T
authors: CT
authors: Wotjak
authors: Inge
authors: I
authors: Sillaber
authors: Florian
authors: F
authors: Holsboer
authors: Wolfgang
authors: W
authors: Wurst
authors: Jan M
authors: JM
authors: Deussing
mesh_terms: D000679:Amygdala / Q000378:metabolism; D000818:Animals; D001007:Anxiety; D001522:Behavior, Animal; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D005239:Fear; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism; D008297:Male; D008568:Memory; D008636:Mesencephalon; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity; D009474:Neurons / Q000378:metabolism*; D017397:Prefrontal Cortex / Q000378:metabolism; D016548:Prosencephalon / Q000166:cytology / Q000378:metabolism; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D009435:Synaptic Transmission; D017557:Ventral Tegmental Area / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism; D000099052:CRF Receptor, Type 1
chemical_list: D018019:Receptors, Corticotropin-Releasing Hormone; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D000099052:CRF Receptor, Type 1; D003346:Corticotropin-Releasing Hormone; D004298:Dopamine