Investigation of the synergistic effects of fluoxetine and probiotics in mice with an experimental depression model

Depression is a psychiatric disorder that profoundly affects mood, cognitive processes, and behavioral patterns, with a multifactorial etiology. Partial or complete non-response to antidepressant treatments necessitates the investigation of alternative therapeutic approaches. This study aimed to comparatively evaluate the single and combined effects of fluoxetine and probiotics on depression-like behaviors. A mouse model in which depression-like behaviors were induced through systemic corticosteroid administration (5 mg/kg) was used in the study. Selected probiotic strains were administered orally on a daily basis, while fluoxetine was applied at a standard dose. The therapeutic effects were assessed using the Forced Swim Test, Tail Suspension Test, and Sucrose Preference Test. Behavioral findings were supported by serum serotonin levels and inflammatory markers (IL-6, TNF-α) measured with the ELISA method. At the end of the treatment period, probiotic administration yielded additional improvements in certain behavioral parameters compared to fluoxetine alone, while the combined treatment produced a more pronounced recovery in helplessness behavior, anhedonia, and stress response. Biochemical analyses indicated increased serotonin levels and decreased inflammatory markers, particularly in the combined treatment group. Consistency was observed between behavioral and physiological changes across all groups. This study demonstrates that probiotics have potential as a complementary option in the treatment of depression. Evidence was obtained suggesting that the combined use of fluoxetine and probiotics may exert a stronger therapeutic effect. The findings indicate that microbiota-based approaches may support existing pharmacological protocols and provide a foundation for future clinical research.