Evaluation of the Combinatory Anti-Depressant Approach of Metformin and Quercetin in Mice Exposed to Chronic Unpredictable Mild Stress Behavorial Alteration

Background To develop a new drug approach, it is necessary to understand possible ways by which suppression of depressive symptoms can be achieved at the biochemical level. One such protein, which can help relieve depression when targeted, is AMP-Activated Protein Kinase (AMPK). The present in vivo study has focussed on AMPK and inflammatory cytokines as potential targets for improving Brain-Derived Neurotrophic Factor levels (BDNF) in depression. Materials and Methods A parallel therapy was administered for standard (Fluoxetine (10 mg/kg), monotherapy (Metformin (200 mg/kg) and Quercetin (20 mg/kg) and combination of half dose (Metformin (100 mg/kg)+Quercetin (10 mg/kg) and full dose (Metformin (200 mg/kg)+Quercetin (20 mg/ kg) for 3 weeks in mice. The study comprises behavorial parameters assessed using locomotor activity, Forced Swimming Test (FST), elevated plus maze, Tail Suspension Test (TST) and Sucrose Preference Test (SPT). Results and Conclusion The results obtained depicted that the high-dose combination doses decreased immobility time, anhedonia and increased open-arm exploration in behavorial tests. Significant difference observed in Metformin (200 mg/kg)+Quercetin (20 mg/ kg) treated group at *p <0.1 [locomotor activity, FST, EPM (dark and open arm) and SPT], ***p <0.01 (TST). Moreover, the combination lowered the number of neurodegenerative cytokines such as Tumour necrosis factor-α, Interlukin-1β, Interlukin-6 (**p <0.05), but Brain Derived Neurotropic Factor (* p <0.1) and corticosterone levels (** p <0.05) were raised indicating antidepressant effects. The studies suggested that metformin and quercetin in combination act as an antidepressant.