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Major depressive disorder (MDD) is a chronic mental illness affecting a wide range of people worldwide. The pathophysiology of MDD is not completely elucidated, but it is believed that oxidative stress and neuroinflammation are involved. In light with this, the aim of the present study was to investigate whether a single administration of the antioxidant 1-methyl-3-(phenylselanyl)-1H-indole (MFSeI) was able to reverse the streptozotocin-induced depression-like behavior, oxidative stress, and neuroinflammation in mice. MFSeI (10 mg/kg) was administered intragastrically (i.g.) 24 h after the intracerebroventricular injection of STZ (0.2 mg/4 μL/per mouse). Thirty minutes after MFSeI administration, behavioral tests and neurochemical analyses were performed. Fluoxetine (10 mg/kg, i.g.) was used as a positive control. MFSeI and fluoxetine were able to reverse the STZ-induced depression-like behavior, as evidenced by decreased immobility time in the forced swimming test and increased grooming time in the splash test. Mechanistically, MFSeI reversed the increased levels of reactive species and lipid peroxidation in the prefrontal cortices and hippocampi of STZ-treated mice. Additionally, neuroinflammation (i.e. expression of NF-κB, IL-1β, and TNF-α) and the reduced mRNA levels of BDNF in the and hippocampi of depressed mice were reversed by treatment with MFSeI. Fluoxetine did not improve the STZ-induced alterations at the levels of reactive species, NF-κB and BDNF in the prefrontal cortices neither the levels of TNF-α in both brain regions. Together, these data suggest that the MFSeI may be a promising compound with antidepressant-like action, reducing oxidative stress and modulating inflammatory pathways in the brain of depressed mice.

Chronic pain and depressive disorders have been estimated to co-occur in up to 80% of patients and traditional antidepressants and analgesics have shown limited clinical efficacy. α- (phenylselanyl) acetophenone (PSAP) is an organic selenium compound which has already demonstrated antioxidant, antidepressant and antinociceptive activities in animal models, without showing acute toxicity. In view of develop more effective treatments to comorbid pain and depression, the purpose of this study was to evaluate the behavioral and biochemical effects of PSAP on reserpine induced pain-depression dyad model in mice as well to analyze the interaction of PSAP with specific targets by molecular docking analysis. Reserpine (0.5 mg/kg daily, for 3 days, i.p.) decreased the latency for the first episode of immobility and the swimming time, as well as increased the immobility time of mice in the modified forced swimming test (mFST). Reserpine also led to a significant decrease in nociceptive threshold in thermal hyperalgesia in the hot plate test. PSAP or imipramine (10 mg/kg daily, for 2 days, i.g.) reversed these alterations in both mFST and hot plate test. Additionaly, PSAP reduced nitrite and malondialdehyde (MDA) levels and catalase (CAT) activity in the cerebral cortex and hippocampus of reserpinised mice. PSAP also normalized monoamine oxidase (MAO-A and MAO-T) activity increased in reserpinised mice. According to the molecular docking analysis, PSAP has affinity to MAO-A, suggesting an inhibition of this enzyme. The data presented here show that PSAP had reversed effects in the pain-depression dyad induced by reserpine, possibly by its antioxidant property and MAO-A inhibition.