Corticotropin-releasing factor receptor 1-deficient mice show decreased anxiety and colonic sensitivity

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 CRF1 receptor antagonism. As CRF1R-deficient mice have an impaired stress response our goal was to further explore the importance of CRF1R in the development of colonic hypersensitivity. Using conscious CRF1R (+/+), CRF1R (+/-) and CRF1R (-/-) mice colonic sensitivity was assessed via a visceromotor behavioural response (VMR) induced by colorectal distension (CRD, 0-60 mmHg). In the CRF1R (+/+) mice there was a pressure-dependent increase in the VMR to CRD that was moderately attenuated in the CRF1R (+/-) mice. However in the CRF1R (-/-) mice a VMR to CRD was only observed at the highest distension pressure (60 mmHg). A CRF1R antagonist, NBI 30775 (30 mg kg(-1) i.p.) significantly decreased the VMR to CRD in CRF1R +/+ mice. An identical inhibitory effect of NBI 30775 was observed in 43% of the CRF1R +/- mice. This study provides pharmacological and genetic evidence for the importance of CRF1R in colonic sensitivity and suggests a link between stress and visceral perception.