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

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.