title: Involvement of the dopaminergic and serotonergic systems in the antidepressant-like effect caused by 4-phenyl-1-(phenylselanylmethyl)-1,2,3-triazole.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Programa de Pós-graduação em Bioquímica (PPGBioq), Universidade Federal do Pampa (Unipampa), Campus Uruguaiana, BR 472 KM 582, Caixa Postal 118, CEP 97500-970 RS, Brazil.
authors.forename: Franciele
authors.initials: F
authors.lastname: Donato
authors.forename: Marcelo Gomes
authors.initials: MG
authors.lastname: de Gomes
authors.forename: André Tiago Rossito
authors.initials: AT
authors.lastname: Goes
authors.forename: Natália
authors.initials: N
authors.lastname: Seus
authors.forename: Diego
authors.initials: D
authors.lastname: Alves
authors.forename: Cristiano Ricardo
authors.initials: CR
authors.lastname: Jesse
authors.forename: Lucielli
authors.initials: L
authors.lastname: Savegnago
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D002374:Catalase / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003863:Depression / Q000188:drug therapy*; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005982:Glutathione Transferase / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009638:Norepinephrine / Q000378:metabolism; D016566:Organoselenium Compounds / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D012701:Serotonin / Q000378:metabolism*; D013997:Time Factors; D023382:Toxicity Tests, Acute; D014230:Triazoles / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity
chemical_list: C584022:4-phenyl-1-(phenylselanylmethyl)-1,2,3-triazole; D000928:Antidepressive Agents; D016566:Organoselenium Compounds; D014230:Triazoles; D012701:Serotonin; D002374:Catalase; D005982:Glutathione Transferase; D004298:Dopamine; D009638:Norepinephrine
keywords: Antidepressant-like; Heterocycles; Mice; Monoaminergic system; Selenium