Su2073 Neonatal Colonic Irritation Produces Persistent Visceral Hypersensitivity and Altered Affective Behavior in a Mouse Model of Irritable Bowel Syndrome (IBS)

Abstract

Introduction: A major theme in functional bowel disorders (FBD) such as irritable bowel syndrome (IBS) is that psychological/psychiatric problems have a pathogenic role, based both on the observation that patients with FBD are more anxious and depressed than healthy control, as well as research linking stress and depression to altered gastrointestinal sensory and motor function. However, recent experimental and epidemiological studies suggest that primary visceral disturbances can lead secondarily to persistent behavioral and emotional abnormalities. The aims of the present study were to test the hypothesis that mild chemical irritation of the colon of neonatal mice can produce changes in visceral hypersensitivity and psychological behaviors that persist into adulthood. Methods: Ten-day old C57BL/6 mouse pups received an intracolonic infusion of 20 μl of 0.5% acetic acid (IBS) or saline (control) to mimic a previously validated model of IBS in rats based on neonatal visceral irritation. Psychological behaviors and pain sensitivity of the colon were assessed when these mice were 8-14 weeks of age. Anxiety-like behaviors were tested using elevated plus maze and open field tests. Depression-like behavior was tested by the forced swim test. Colonic hypersensitivity to graded colorectal balloon distension (15, 30, 50 and 70mmHg) was determined by visceromotor responses (VMR) measured by electromyography of external oblique muscle. Resutls: Neonatal colorectal infusion of acetic acid but not saline significantly increased electromyographic activity in response to all of pressure colorectal distension in adults, suggesting the persistence of colonic hypersensitivity. In the elevated plus maze and open field tests, IBS mice showed a significant reduction in time spent in the open arms of elevated plus maze (control: 73.04±5.26s vs IBS: 53.54±6.53s, p<0.05) and in the center of the open field (control: 73.99±6.42s vs IBS: 37.32±4.62s, p<0.05), suggesting an anxietylike phenotype. IBS mice also showed a significant increase in immobility in the forced swim test (control: 90.05±12.08s vs IBS: 140.43±20.06s, p<0.05), suggesting an increase in depression-like behavior. Conclusion: The present results demonstrate that transient colonic irritation in the neonatal period can induce long-lasting depression-like and anxietylike behaviors. These findings provide a new paradigm for the psychological co-morbidity in functional bowel disorders.