Involvement of the dopaminergic and serotonergic systems in the antidepressant-like effect caused by 4-phenyl-1-(phenylselanylmethyl)-1,2,3-triazole.

Aims: The study investigated the antidepressant-like effect and acute toxicity of 4-phenyl-1-(phenylselanylmethyl)-1,2,3-triazole (Se-TZ), an organoselenium-containing heterocycle compound in mice.

Main Methods: The antidepressant-like effect of Se-TZ (1-50mg/kg) and its mechanism of action, was analyzed in the tail suspension test (TST) in male C57BL/6J mice. Additionally, the levels of the monoamines and their metabolites in cerebral cortex and hippocampus were analyzed by high-performance liquid chromatography. To investigate the potential acute toxicity caused by Se-TZ, the mice received a single oral dose of Se-TZ (1-50mg/kg), and after 72h were performed the assays.

Key Findings: The Se-TZ (5-50mg/kg) significantly reduced immobility time in TST without altering locomotor and exploratory activities. The antidepressant-like effect of Se-TZ (25mg/kg) in the TST was prevented by pre-treatment of mice with SCH23390, sulpiride and methysergide, but not with prazosin, yohimbine and propranolol. Se-TZ, increased monoamine neurotransmitters dopamine and serotonin levels in the cerebral cortex and hippocampus, whereas norepinephrine turnover was not changed. This study also demonstrated that the Se-TZ, did not cause the acute toxicity in biochemical markers hepatic and renal investigated. The results evidenced that exposure to Se-TZ caused a significant increase in the catalase (CAT) activity in the cerebral cortex and hippocampus, however the glutathione S-transferase (GST) activity increased only in the cerebral cortex.

Significance: These results suggest that Se-TZ demonstrated antidepressant-like effect, mediated via the central dopaminergic and serotoninergic neurotransmitter systems which may be of interest as a therapeutic agent for the treatment of depressive disorders.