TY - JOUR
T1 - Deletion of Crhr2 reveals an anxiolytic role for corticotropin-releasing hormone receptor-2
AU - Kishimoto, Toshimitsu
AU - Radulovic, Jelena
AU - Radulovic, Marko
AU - Lin, Chijen R.
AU - Schrick, Christina
AU - Hooshmand, Farideh
AU - Hermanson, Ola
AU - Rosenfeld, Michael G.
AU - Spiess, Joachim
N1 - Funding Information:
We thank M. Ayers, M. Fisher, C. Todorovic, K. Eckart, T. Liepold and A. Burgdorf for discussions and assistance. O.H. is supported by the Swedish Brain Foundation. M.G.R. is an investigator with the Howard Hughes Medical Institute. This work is supported by NIH grants to M.G.R. and MPG funds to J.S.
PY - 2000/4
Y1 - 2000/4
N2 - Corticotropin-releasing hormone (Crh), a 41-residue polypeptide, activates two G-protein-coupled receptors, Crhr1 (refs 3-5) and Crhr2 (refs 6-9), causing (among other transductional, events) phosphorylation of the transcription factor Creb (ref. 10). The physiologic role of these receptors is only partially understood. Here we report that male, but not female, Crhr2-deficient mice exhibit enhanced anxious behaviour in several tests of anxiety in contrast to mice lacking Crhr1 (refs 11,12). The enhanced anxiety of Crhr2-deficient mice is not due to changes in hypothalamic-pituitary- adrenal (HPA) axis activity, but rather reflects impaired responses in specific brain regions involved in emotional and autonomic function, as monitored by a reduction of Creb phosphorylation in male, but not female, Crhr2(-/-) mice. We propose that Crhr2 predominantly mediates a central anxiolytic response, opposing the general anxiogenic effect of Crh mediated by Crhr1. Neither male nor female Crhr2-deficient mice show alterations of baseline feeding behaviour. Both respond with increased edema-formation in response to thermal exposure, however, indicating that in contrast to its central role in anxiety, the peripheral role of Crhr2 in vascular permeability is independent of gender.
AB - Corticotropin-releasing hormone (Crh), a 41-residue polypeptide, activates two G-protein-coupled receptors, Crhr1 (refs 3-5) and Crhr2 (refs 6-9), causing (among other transductional, events) phosphorylation of the transcription factor Creb (ref. 10). The physiologic role of these receptors is only partially understood. Here we report that male, but not female, Crhr2-deficient mice exhibit enhanced anxious behaviour in several tests of anxiety in contrast to mice lacking Crhr1 (refs 11,12). The enhanced anxiety of Crhr2-deficient mice is not due to changes in hypothalamic-pituitary- adrenal (HPA) axis activity, but rather reflects impaired responses in specific brain regions involved in emotional and autonomic function, as monitored by a reduction of Creb phosphorylation in male, but not female, Crhr2(-/-) mice. We propose that Crhr2 predominantly mediates a central anxiolytic response, opposing the general anxiogenic effect of Crh mediated by Crhr1. Neither male nor female Crhr2-deficient mice show alterations of baseline feeding behaviour. Both respond with increased edema-formation in response to thermal exposure, however, indicating that in contrast to its central role in anxiety, the peripheral role of Crhr2 in vascular permeability is independent of gender.
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U2 - 10.1038/74271
DO - 10.1038/74271
M3 - Article
C2 - 10742109
AN - SCOPUS:0034069655
SN - 1061-4036
VL - 24
SP - 415
EP - 419
JO - Nature Genetics
JF - Nature Genetics
IS - 4
ER -