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Corticotropin‐releasing factor receptor 1‐deficient mice show decreased anxiety and colonic sensitivity
Author(s) -
Trimble N.,
Johnson A. C.,
Foster A.,
Greenwoodvan Meerveld B.
Publication year - 2007
Publication title -
neurogastroenterology and motility
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.489
H-Index - 105
eISSN - 1365-2982
pISSN - 1350-1925
DOI - 10.1111/j.1365-2982.2007.00951.x
Subject(s) - anxiety , receptor , sensitivity (control systems) , medicine , anxiety sensitivity , psychology , irritable bowel syndrome , endocrinology , psychiatry , electronic engineering , engineering
Corticotropin releasing factor (CRF) is an important mediator in the stress response. Previous studies in rodent models demonstrated that stress‐induced colonic hypersensitivity was inhibited by CRF 1 receptor antagonism. As CRF 1 R‐deficient mice have an impaired stress response our goal was to further explore the importance of CRF 1 R in the development of colonic hypersensitivity. Using conscious CRF 1 R (+/+), CRF 1 R (+/−) and CRF 1 R (−/−) mice colonic sensitivity was assessed via a visceromotor behavioural response (VMR) induced by colorectal distension (CRD, 0–60 mmHg). In the CRF 1 R (+/+) mice there was a pressure‐dependent increase in the VMR to CRD that was moderately attenuated in the CRF 1 R (+/−) mice. However in the CRF 1 R (−/−) mice a VMR to CRD was only observed at the highest distension pressure (60 mmHg). A CRF 1 R antagonist, NBI 30775 (30 mg kg −1 i.p.) significantly decreased the VMR to CRD in CRF 1 R +/+ mice. An identical inhibitory effect of NBI 30775 was observed in 43% of the CRF 1 R +/− mice. This study provides pharmacological and genetic evidence for the importance of CRF 1 R in colonic sensitivity and suggests a link between stress and visceral perception.