Yeast supplementation potentiates fluoxetine's anti-depressant effect in mice via modulation of oxido-inflammatory, CREB, and MAPK signaling pathways.

Introduction: The therapeutic potential of yeast in the management of depression is unknown. Thus, we evaluated the modulatory effect of nutritional yeast supplementation on antidepressant activity of fluoxetine in mice models of depressive-like behaviors (DLB). Methods: A total of 112 mice were divided into 16 groups (n = 7 each) for a 3-stage study. Stage I (non-DLB study) had groups Ia (10 mL/kg vehicle), Ib (20 mg/kg fluoxetine), Ic - If (2% yeast diet for all, but Id - If additionally received 5 mg/kg, 10 mg/kg, and 20 mg/kg fluoxetine respectively). Stage II (lipopolysaccharide [LPS] model of DLB) had groups IIa - IIb (10 mL/kg vehicle), IIc (20 mg/kg fluoxetine), IId (yeast) and IIe (yeast + 20 mg/kg fluoxetine). After these treatments for 24 days, animals in IIb - IIe received 0.83 mg/kg of LPS on the 25th day. Except for group IIIa (10 mL/kg vehicle), animals in other groups of stage III (unpredictable chronic mild stress [UCMS] model) were exposed to UCMS for 24 days along with 10 mL/kg vehicle (IIIb), 20 mg/kg fluoxetine (IIIc), yeast (IIId), or yeast + fluoxetine (IIIe). Results: Yeast and fluoxetine attenuated LPS- and UCMS-induced immobility, derangement of oxido-inflammatory (TNF-α, IL-6, NO, MDA, SOD, GSH, CAT, and AChE) and CREB/MAPK pathways. While fluoxetine had more potent effect than yeast when used separately, pre-treatment of mice with their combination had more pronounced effect than either of them. Conclusion: Yeast supplementation improves the antidepressant activity of fluoxetine in mice by modulating oxido-inflammatory, CREB, and MAPK pathways.