2-Phenyl-3-(phenylselanyl)benzofuran elicits acute antidepressant-like action in male Swiss mice mediated by modulation of the dopaminergic system and reveals therapeutic efficacy in both sexes

Rationale Depression is a psychiatric disorder that constitutes one of the leading causes of disability worldwide. 2-Phenyl-3-(phenylselanyl)benzofuran (SeBZF 1 ) has been studied as a potential antidepressant drug, but its pharmacological action needs more investigation. Objectives and methods Our aim was to extend information about the antidepressant-like action of SeBZF 1 using the mouse tail suspension test (TST). Initial experiments investigated the mechanisms involved in the acute antidepressant-like action of SeBZF 1 in male Swiss mice. For this purpose, males received noradrenergic or dopaminergic receptor antagonists before acute SeBZF 1 administration (50 mg/kg, per oral). In parallel, effects of combined treatment with SeBZF 1 and bupropion at sub-effective doses (1 and 3 mg/kg, respectively) were tested. The next experiments were designed to determine the acute effects of SeBZF 1 in females through a dose–response curve (5–50 mg/kg). Lastly, the efficacy of a 7-day repeated treatment with SeBZF 1 (1 and 5 mg/kg) in mice of both sexes and its safety were evaluated. TST and the open-field test (OFT) were employed in all behavioral experiments. Results Pre-administration of dopaminergic antagonists (SCH23390, a selective D 1 R antagonist; sulpiride, a selective D 2 /D 3 R antagonist; and haloperidol, a non-selective antagonist), but not of adrenergic α 1 , α 2 , and β-R antagonists, blocked the acute antidepressant-like effects of SeBZF 1 in males. Co-administration of sub-effective doses of SeBZF 1 and bupropion reduced the depressive phenotype. In addition, acute treatment with SeBZF 1 at 50 mg/kg produced a reduction of female immobility. Finally, repeated treatment with SeBZF 1 (1 and 5 mg/kg) was effective in causing antidepressant-like effects in both sexes. Locomotor activity, plasma transaminases, and urea levels remained unaltered after SeBZF 1 exposure. Conclusion Our findings provide evidence of the involvement of the dopaminergic system in the acutely antidepressant-like action of SeBZF 1 in male mice and reveal the compound efficacy when acute or repeatedly administered in both sexes.