LX-2931

1-(2-(4-(4-ethylphenyl)-1H-1,2,3-triazol-1-yl)phenyl)ethanone (ETAP) is a novel hybrid compound containing 1,2,3-triazole and acetophenone. It exhibits antidepressant-like effects in male mice, linked to modulation of serotonergic receptors and monoamine oxidase A (MAO-A) inhibition. This study aimed to evaluate the involvement of the dopaminergic and noradrenergic systems, as well as MAO-B activity inhibition, in the antidepressant-like effect of ETAP in male mice, and to evaluate the antidepressant-like effect of ETAP in female mice. Male mice were treated with different dopaminergic and noradrenergic receptors antagonists 15 min before administering ETAP (1 mg/kg, intragastrically, i.g.). The tail suspension test (TST) was performed 30 minutes later. Different male mice were treated with ETAP (1 mg/kg, i.g.), and 30 minutes later, were euthanized to assess MAO-B activity in the prefrontal cortex and hippocampus. To evaluate the antidepressant-like of ETAP in female mice, ETAP (1 mg/kg, i.g.) was administered, followed by the TST and the forced swimming test (FST) 30 minutes later. The dopaminergic antagonists haloperidol (0.05 mg/kg, intraperitoneally, i.p.), SCH23390 (0.01 mg/kg, subcutaneously, s.c.), and sulpiride (50 mg/kg, i.p.), as well the noradrenergic antagonists prazosin (1 mg/kg, i.p.), yohimbine (1 mg/kg, i.p.), and propranolol (2 mg/kg, i.p.), prevented the antidepressant-like effect of ETAP in the TST. MAO-B activity was unaffected by ETAP in both the prefrontal cortex and hippocampus. ETAP (1 mg/kg, i.g.) induced a significant antidepressant-like effect in female mice in the TST and FST. These findings provide valuable insights into the antidepressant-like effect of ETAP, highlighting its potential for developing more effective depression treatments.