alpha- (phenylselanyl) acetophenone mitigates reserpine-induced pain-depression dyad: Behavioral, biochemical and molecular docking evidences

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. alpha- (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.