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1 CRF Research Program, Department of Medicine, David Geffen School of Medicine, Center for Neurovisceral Sciences & Women's Health and CURE: Digestive Diseases Research Center, Department of Medicine, Los Angeles, CA, USA; GLA VA Healthcare System, Los Angeles, CA, USA
2 Department of Psychology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
3 Stress Neurobiology Laboratory, Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA
4 CRF Research Program, Department of Medicine, David Geffen School of Medicine, Center for Neurovisceral Sciences & Women's Health and CURE: Digestive Diseases Research Center, Department of Medicine, Los Angeles, CA, USA; Department of Physiology and Psychiatry & Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA; GLA VA Healthcare System, Los Angeles, CA, USA
* To whom correspondence should be addressed. E-mail: emayer{at}ucla.edu.
Background: In rodents, maternal pup interactions play an important role in programming the stress responsiveness of the adult organism. Aims: 1) To determine the effect of different neonatal rearing conditions on acute and delayed stress-induced visceral sensitivity, as well as on other measures of stress sensitivity of the adult animal. 2) To determine the role of corticotropin releasing factor receptor subtype 1 (CRF1R) in mediating visceral hypersensitivity. Methods: Three groups of male Long Evans rat pups were used: separation from their dam for 180 min daily from post-natal day 2 to 14 (MS180), daily separation (handling) for 15 min (H), or no handling (NH). The visceromotor response (VMR) to colorectal distension, stress-induced colonic motility and anxiety-like behavior were assessed in the adult rats. The VMR was assessed at baseline, immediately after a 1-h water avoidance (WA) stress, and 24 h post-stress. Astressin B, a non-selective CRF receptor (CRF-R) antagonist, or CP-154,526, a selective CRF1R antagonist, was administered before the stressor and/or before the 24 h measurement. Results: MS rats developed acute and delayed stress-induced visceral hyperalgesia. In contrast, H rats showed hypoalgesia immediately after WA and no change in VMR on day 2. MS rats with visceral hyperalgesia also exhibited enhanced stress-induced colonic motility and increased anxiety-like behavior. In MS rats, both CRF-R antagonists abolished acute and delayed increases in VMR. Conclusions: 1) Rearing conditions have a significant effect on adult stress responsiveness including immediate and delayed visceral pain responses to an acute stressor. 2) Both acute and delayed stress-induced visceral hypersensitivity in MS rats are mediated by the CRF/CRF1R system.
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