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

Abstract

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. 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. Male Swiss mice were treated with CF3SePB (1-50mg/kg, i.g.) and 30min 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, 100mg/kg, i.p.) or the receptor antagonists WAY100635 (0.1mg/kg, s.c., a 5-HT1A receptor antagonist), ketanserin (1mg/kg, i.p., a 5-HT2A/2C receptor antagonist), ondansetron (1mg/kg, i.p., a 5-HT3 receptor antagonist), GR110838 (0.1mg/kg, i.p., a 5-HT4 receptor antagonist), prazosin (1mg/kg, i.p., an α1-adrenergic receptor antagonist), yohimbine (1mg/kg, i.p., an α2-adrenergic receptor antagonist) and propranolol (2mg/kg, i.p., a non-selective beta-adrenergic receptor antagonist) at specific times before CF3SePB (50mg/kg, i.g.), and after 30min of CF3SePB administration the FST was performed. 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-HT1A 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. This study pointed a new compound with antidepressant-like effect, and it could be considered for the development of new antidepressants.