TY - JOUR AU - Ghia, Jean-Eric AU - Blennerhassett, Patricia AU - Collins, Stephen M. T1 - Impaired parasympathetic function increases susceptibility to inflammatory bowel disease in a mouse model of depression PY - 2008/06/02/ AB - Clinical and experimental evidence indicates that intestinal inflammatory conditions can be exacerbated by behavioral conditions such as depression. The recent demonstration of a tonic counterinflammatory influence mediated by the vagus nerve in experimental colitis provides a potential link between behavior and gut inflammation. Here we show that experimental conditions that induced depressive-like behaviors in mice increased susceptibility to intestinal inflammation by interfering with the tonic vagal inhibition of proinflammatory macrophages and that tricyclic antidepressants restored vagal function and reduced intestinal inflammation. These results show that reserpine-induced monoamine depletion and maternal separation, 2 models for depression, produced a vulnerability to colitis by a mechanism involving parasympathetic transmission and the presence of gut macrophages. The tricyclic antidepressant desmethylimipramine protected against this vulnerability by a vagal-dependent mechanism. Together these results illustrate the critical role of the vagus in both the vulnerability to inflammation induced by depressive-like conditions and the protection afforded by tricyclic antidepressants and rationalize a clinical evaluation of both parasympathomimetics and tricyclic antidepressants in treatment of inflammatory bowel disease. JF - The Journal of Clinical Investigation JA - J Clin Invest SN - 0021-9738 DO - 10.1172/JCI32849 VL - 118 IS - 6 UR - https://doi.org/10.1172/JCI32849 SP - 2209 EP - 2218 PB - The American Society for Clinical Investigation ER -