Journal
AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY
Volume 292, Issue 4, Pages R1429-R1438Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpregu.00626.2006
Keywords
chronic stress; colon; urine; locomotor activity; astressin B; mouse urocortin 2
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Funding
- NIDDK NIH HHS [R01 DK-57238, R21 DK-068155, R01 DK033061, R01 DK057238, R01 DK-33061, DK-26741, P50 DK064539, R21 DK068155, P01 DK026741, P50 DK-64539] Funding Source: Medline
- NIMH NIH HHS [R01 MH065689, R01 MH-65689] Funding Source: Medline
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Acute stress affects gut functions through the activation of corticotropin-releasing factor (CRF) receptors. The impact of acute stress on pelvic viscera in the context of chronic stress is not well characterized. We investigated the colonic, urinary, and locomotor responses monitored as fecal pellet output (FPO), urine voiding, and ambulatory activity, respectively, in female and male CRF-overexpressing (CRF-OE) mice, a chronic stress model, and their wild-type littermates (WTL). Female CRF-OE mice, compared with WTL, had enhanced FPO to 2-min handling (150%) and 60-min novel environment (155%) but displayed a similar response to a 60-min partial restraint stress. Female CRF-OE mice, compared with WTL, also had a significantly increased number of urine spots (7.3 +/- 1.4 vs. 1.3 +/- 0.8 spots/h) and lower locomotor activity (246.8 +/- 47.8 vs. 388.2 +/- 31.9 entries/h) to a novel environment. Male CRF-OE mice and WTL both responded to a novel environment but failed to show differences between them in colonic and locomotor responses. Male WTL, compared with female WTL, had higher FPO (113%). In female CRF-OE mice, the CRF1/CRF2 receptor antagonist astressin B and the selective CRF2 receptor agonist mouse urocortin 2 (injected peripherally) prevented the enhanced defecation without affecting urine or locomotor responses to novel environment. RT-PCR showed that CRF1 and CRF2 receptors are expressed in the mouse colonic tissues. The data show that chronic stress, due to continuous central CRF overdrive, renders female CRF-OE mice to have enhanced pelvic and altered behavioral responses to superimposed mild stressors and that CRF1-initiated colonic response is counteracted by selective activation of CRF2 receptor.
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