Dopaminergic receptors involvement in the antidepressant-like effect of N-(3-((3-(trifluoromethyl)phenyl)selanyl)prop-2-yn-1-yl) benzamide in mice

Abstract

Major Depressive Disorder (MDD) directly impacts the lives of countless individuals worldwide, yet its causes remain incompletely understood. However, it is recognized that a deficiency in monoamines, including dopamine, may contribute to this disorder. N-(3-((3-(trifluoromethyl)phenyl)selenyl)prop-2-yn-1-yl) (CF₃SePB) is an organoselenium compound that presented antidepressant-like effect in mice related to modulation of serotonergic, but not noradrenergic system. To expand the knowledge about CF₃SePB mechanisms of action, this study aimed to evaluate the involvement of dopaminergic system in its antidepressant-like effect. Male Swiss mice were pre-treated with the haloperidol (0.05 mg/kg, i.p., a non-selective D₂ receptor antagonist), SCH 23390 (0.01 mg/kg, s.c., a D₁ receptor antagonist), and sulpiride (50 mg/kg, i.p., a D₂ receptor antagonist) 15 min before CF₃SePB (50 mg/kg, i.g.), and after 30 min of CF₃SePB administration the forced swimming test (FST) was performed. CF₃SePB presented an anti-immobility effect in the FST, demonstrated by increase in the latency to first episode of immobility and reduction of total immobility of mice, and the pre-treatment of mice with haloperidol, SCH 23390 and sulpiride prevented these effects, showing that the antidepressant-like effect of CF₃SePB is related to the modulation of the dopaminergic system, specifically the D₁ and D₂ receptors. In addition, in silico pharmacokinetic profiling of CF₃SePB predicted its low likelihood of inducing adverse effects and potential to cross the blood–brain barrier. These results expand the understanding of CF₃SePB mechanisms for its antidepressant-like effect, reinforcing the potential of this organonoselenium compound for developing new antidepressants.