Deletion of Crhr2 reveals an anxiolytic role for corticotropin-releasing hormone receptor-2

Toshimitsu Kishimoto, Jelena Radulovic*, Marko Radulovic, Chijen R. Lin, Christina Schrick, Farideh Hooshmand, Ola Hermanson, Michael G. Rosenfeld, Joachim Spiess

*Corresponding author for this work

Research output: Contribution to journalArticle

435 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)415-419
Number of pages5
JournalNature Genetics
Volume24
Issue number4
DOIs
StatePublished - Apr 1 2000

ASJC Scopus subject areas

  • Genetics

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    Kishimoto, T., Radulovic, J., Radulovic, M., Lin, C. R., Schrick, C., Hooshmand, F., Hermanson, O., Rosenfeld, M. G., & Spiess, J. (2000). Deletion of Crhr2 reveals an anxiolytic role for corticotropin-releasing hormone receptor-2. Nature Genetics, 24(4), 415-419. https://doi.org/10.1038/74271