Antidepressants attenuate increased susceptibility to colitis in a murine model of depression.
OBJECTIVE
Psychiatric factors may determine gastrointestinal health outcomes. Here, we used a model of depression based on neonatal maternal separation (MS) to identify alterations in gut physiology and to assess its association with increased sensitivity to experimental colitis in adulthood. We also examined whether antidepressant therapy attenuates the increased susceptibility to colitis.


METHODS
C57BL/6 mouse pups were separated from mothers for 3 hours per day at 1-21 days of age. Maternally unseparated (US) litters served as controls. At 8 weeks of age mice were examined for changes in behavior, intestinal permeability, and sensitivity to colitis. Separate sets of MS and US mice were given either saline or the antidepressant desipramine 15 mg/kg once daily at 23-36 days of age. Testing of mice occurred at 8 weeks of age.


RESULTS
Adult MS mice showed evidence of depressive-like behavior and enhanced intestinal permeability but showed no evidence of spontaneous inflammation. A more severe colitis was seen in MS compared with US mice. Antidepressant therapy improved parameters of depressive-like behavior and reduced the vulnerability to dextran sulphate sodium colitis in MS mice but had no effect on colitis in US mice.


CONCLUSIONS
MS may lead to depression and increased responsiveness to stress, to impaired intestinal barrier function, and to enhanced vulnerability to colitis in adulthood. This vulnerability is reversed by antidepressant therapy. Depression increases vulnerability to intestinal inflammation. We speculate that pre-existing depression may facilitate the expression of inflammatory bowel diseases.
Varghese
Ashwin K
AK
Intestinal Diseases Research Program, McMaster University, Hamilton, Ontario, Canada.
Verdú
Elena F
EF
Bercik
Premysl
P
Khan
Waliul I
WI
Blennerhassett
Patricia A
PA
Szechtman
Henry
H
Collins
Stephen M
SM
D000818:Animals; D000831:Animals, Newborn; D000928:Antidepressive Agents / Q000494:pharmacology*; D003092:Colitis / Q000517:prevention & control* / Q000523:psychology*; D016207:Cytokines / Q000378:metabolism; D003863:Depression / Q000188:drug therapy* / Q000503:physiopathology; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005769:Gastrointestinal Motility / Q000187:drug effects / Q000502:physiology; D018836:Inflammation Mediators / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D011336:Probability; D011897:Random Allocation; D012016:Reference Values; D012307:Risk Factors; D012680:Sensitivity and Specificity
D000928:Antidepressive Agents; D016207:Cytokines; D018836:Inflammation Mediators