Vortioxetine improves gastrointestinal motility and reduces intestinal inflammation in a cuprizone-induced multiple sclerosis model in mice

Abstract

Aim: To investigate the effects of vortioxetine on gastrointestinal motility and intestinal inflammation in a cuprizone-induced demyelination model in mice by evaluating pro-inflammatory cytokine responses.

Materials and Methods: Twenty-one C57Bl/6 mice (8 weeks old) were randomly allocated into three groups: Control, cuprizone, and cuprizone + vortioxetine (n = 7/group). Demyelination was induced by oral gavage of cuprizone (10 mg/kg) every other day for 5 weeks. Vortioxetine (10 mg/kg/day) was administered intraperitoneally for 5 weeks. Gastrointestinal motility was assessed by 24-hour fecal pellet count and wet fecal weight. At the end of the protocol, TNF-α and IL-1β levels in the stomach, intestine, and colon were measured by ELISA.

Results: Cuprizone administration significantly reduced fecal pellet output and wet fecal weight compared with controls (p<0.0001). Vortioxetine treatment restored both parameters toward control levels (p<0.01). Intestinal TNF‑α and IL‑1β levels were markedly increased in the cuprizone group (p<0.0001) and were significantly decreased following vortioxetine treatment, reaching near-control values. Similar reductions were observed in colonic cytokine levels, whereas gastric cytokines were largely unaffected.

Conclusion: Vortioxetine improves gastrointestinal motility and attenuates intestinal and colonic pro-inflammatory cytokine expression in a cuprizone-induced demyelination model in mice. These findings suggest that vortioxetine has the potential to exert beneficial effects on the gastrointestinal function and highlight its potential as an adjunctive therapy for gastrointestinal comorbidities in multiple sclerosis.