N-(3-((3-(trifluoromethyl)phenyl)selanyl)prop-2-yn-1-yl) benzamide induces antidepressant-like effect in mice: involvement of the serotonergic system

Abstract

Rationale: Major Depressive Disorder (MDD) significantly impairs the quality of life for those affected. While the exact causes of MDD are not fully understood, the deficit of monoamines, especially serotonin and noradrenaline, is widely accepted. Resistance to long-term treatments and adverse effects are often observed, highlighting the need for new pharmacological therapies. Synthetic organic compounds containing selenium have exhibited pharmacological properties, including potential antidepressant effects.

Objective: To evaluate the antidepressant-like effect of N-(3-((3-(trifluoromethyl)phenyl)selenyl)prop-2-yn-1-yl) benzamide (CF₃SePB) in mice and the involvement of the serotonergic and noradrenergic systems.

Methods: Male Swiss mice were treated with CF₃SePB (1-50 mg/kg, i.g.) and 30 min later the forced swimming test (FST) or tail suspension test (TST) was performed. To investigate the involvement of the serotonergic and noradrenergic systems in the antidepressant-like effect of CF₃SePB, mice were pre-treated with p-CPA (a 5-HT depletor, 100 mg/kg, i.p.) or the receptor antagonists WAY100635 (0.1 mg/kg, s.c., a 5-HT_1A receptor antagonist), ketanserin (1 mg/kg, i.p., a 5-HT_2A/2C receptor antagonist), ondansetron (1 mg/kg, i.p., a 5-HT₃ receptor antagonist), GR110838 (0.1 mg/kg, i.p., a 5-HT₄ receptor antagonist), prazosin (1 mg/kg, i.p., an α₁-adrenergic receptor antagonist), yohimbine (1 mg/kg, i.p., an α₂-adrenergic receptor antagonist) and propranolol (2 mg/kg, i.p., a non-selective beta-adrenergic receptor antagonist) at specific times before CF₃SePB (50 mg/kg, i.g.), and after 30 min of CF₃SePB administration the FST was performed.

Results: CF₃SePB showed an antidepressant-like effect in both FST and TST and this effect was related to the modulation of the serotonergic system, specially the 5-HT_1A and 5-HT₃ receptors. None of the noradrenergic antagonists prevented the antidepressant-like effect of CF₃SePB. The compound exhibited a low potential for inducing acute toxicity in adult female Swiss mice.

Conclusion: This study pointed a new compound with antidepressant-like effect, and it could be considered for the development of new antidepressants.

Keywords: Benzamide; Depression; Mice; Noradrenergic system; Selenium; Serotonergic system.