Opioid System Contributes to the Trifluoromethyl-Substituted Diselenide Effectiveness in a Lifestyle-Induced...

Energy-dense foods and ethanol consumption are associated with mood disorders. m-Trifluoromethyl-diphenyl diselenide [(m-CF₃-PhSe)₂] has been a prominent pharmacological target due to its antidepressant-like effects. This study investigated if the modulation of opioid and glucocorticoid receptors and its well-known antioxidant property contribute to the (m-CF₃-PhSe)₂ antidepressant-like effect in young mice subjected to an energy-dense diet and ethanol intake. Swiss male mice [postnatal day (PND) 25] were exposed to an energy-dense diet (containing 20% fat and 20% carbohydrate) or standard chow until the PND 67. Mice received ethanol (2 g/kg) or water administration (3 times a week, intragastrically [i.g.]) from PND 45 to PND 60. After that, mice received (m-CF₃-PhSe)₂ (5 mg/kg/day; i.g) or vegetal oil administration from PND 60 to 66. Mice performed the behavioral tests to evaluate the depressive-like phenotype. The results showed that individually neither an energy-dense diet nor ethanol group induced a depressive-like phenotype, but the association of both induced this phenotype in young mice. Oxidative stress was characterized by the increase of malondialdehyde, the decrease in the superoxide dismutase activity, and non-protein sulfhydryl levels in the cerebral cortex of depressive-like mice. Depressive-like mice showed an increase in the protein levels of opioid receptors and depletion in those of glucocorticoid. (m-CF₃-PhSe)₂ abolished depressive-like phenotype and oxidative stress as well as modulated the levels of glucocorticoid and opioid receptors. In conclusion, the modulation of opioid and glucocorticoid receptors and the antioxidant property contributed to the (m-CF₃-PhSe)₂ antidepressant-like effect in young mice exposed to an energy-dense diet and ethanol intake.