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 CRF(1)R-deficient mice have (+/+), 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 CRF1R (+/-) 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.
Trimble
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N
Oklahoma Center for Neuroscience, University of Oklahoma Health Science Center, OK, USA.
Johnson
A C
AC
Foster
A
A
Greenwood-van Meerveld
B
B
D000818:Animals; D001007:Anxiety / Q000378:metabolism* / Q000503:physiopathology; D003106:Colon / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D004576:Electromyography; D005260:Female; D008297:Male; D008365:Manometry; D051379:Mice; D018345:Mice, Knockout; D017288:Pain Threshold / Q000187:drug effects; D011743:Pyrimidines / Q000494:pharmacology; D018019:Receptors, Corticotropin-Releasing Hormone / Q000172:deficiency*; D013315:Stress, Psychological / Q000378:metabolism / Q000503:physiopathology; D000099052:CRF Receptor, Type 1
D011743:Pyrimidines; C412383:R 121919; D018019:Receptors, Corticotropin-Releasing Hormone; D000099052:CRF Receptor, Type 1