Fluoxetine Ameliorates the Aggravation of UC Symptoms in C57BL/6 Mice Induced by CUMS

Curr Med Sci. 2023 Oct;43(5):1033-1042. doi: 10.1007/s11596-023-2743-4. Epub 2023 Aug 29.

Abstract

Objective: Patients with chronic ulcerative colitis (UC) often have mental symptoms such as depression and anxiety, and stress can lead to gastrointestinal diseases. However, the correlation between mental stress and UC is unclear. In this paper, chronic unpredictable mild stress (CUMS) was utilized to evaluate the involvement of mental factors in the pathogenesis of UC.

Methods: The CUMS model was used to evaluate the direct/indirect involvement of mental factors in the pathogenesis of UC. The behavior was evaluated by the open field, forced swimming, and tail suspension tests. Body weight, the disease activity index (DAI) score, colon length, and HE staining of colon tissue were used to evaluate the action of CUMS and fluoxetine.

Results: The results showed that weight loss and the DAI score increased in CUMS mice, but they had no meaningful effect on colon length and morphological structure of colon tissue. However, CUMS aggravated dextran sulfate sodium (DSS)-induced colon length shortening and colon morphological structure damage. Fluoxetine significantly improved the DAI score, shortened colon length, and damaged morphology and structure of the colons induced by CUMS combined with DSS in mice. Fluoxetine also decreased the level of IL-6 in the serum and the TNF-α and IFN-γ levels of colon tissue. Fluoxetine simultaneously improved behavioral abnormalities induced by CUMS combined with DSS in mice.

Conclusion: CUMS aggravated the UC symptoms induced by DSS, and fluoxetine could improve the UC symptoms due to its improvement in the inflammatory level and behavioral abnormalities.

Keywords: behavior; chronic unpredictable mild stress; dextran sulfate sodium; fluoxetine; ulcerative colitis.