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

  1. N. Trimble1,
  2. A. C. Johnson1,
  3. A. Foster2,
  4. B. Greenwood-van Meerveld1,3

Article first published online: 21 MAY 2007

DOI: 10.1111/j.1365-2982.2007.00951.x

Issue

Neurogastroenterology & Motility

Neurogastroenterology & Motility

Volume 19, Issue 9, pages 754–760, September 2007

Additional Information

How to Cite

Trimble, N., Johnson, A. C., Foster, A. and Greenwood-van Meerveld, B. (2007), Corticotropin-releasing factor receptor 1-deficient mice show decreased anxiety and colonic sensitivity. Neurogastroenterology & Motility, 19: 754–760. doi: 10.1111/j.1365-2982.2007.00951.x

Author Information

  1. 1

    *Oklahoma Center for Neuroscience, University of Oklahoma Health Science Center, OK, USA

  2. 2

    Neurocrine Biosciences, San Diego, CA, USA

  3. 3

    VA Medical Center, University of Oklahoma Health Science Center, OK, USA

*Beverley Greenwood-Van Meerveld PhD, FACG, V.A. Medical Center, Research Admin. Rm. 151, 921 N.E. 13th St, Oklahoma City, OK 73104, USA. Tel: +1 405 270 0501 ext. 3547; fax: +1 405 290 1719; e-mail: beverley-greenwood@ouhsc.edu

Publication History

  1. Issue published online: 21 MAY 2007
  2. Article first published online: 21 MAY 2007
  3. Received: 11 December 2006 Accepted for publication: 28 March 2007

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Keywords:

  • anxiety;
  • colon;
  • mouse;
  • stress;
  • visceral pain

Abstract  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.

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