Contribution of serotonergic and nitrergic pathways, as well as monoamine oxidase-a and Na+, K+-ATPase enzymes in antidepressant-like action of ((4-tert-butylcyclohexylidene) methyl) (4-methoxystyryl) sulfide (BMMS)

  • Renata L. de Oliveira
  • Guilherme T. Voss
  • Jaini J. Paltian
  • Mikaela P. Pinz
  • Marina Laura C. P. Torres
  • Michele P. Moreira
  • Marina C. Dilelio
  • Claudio C. Silveira
  • Ethel A. WilhelmEmail author
  • Cristiane LucheseEmail author
Original Article


The present study investigated a possible antidepressant-like effect of ((4-tert-butylcyclohexylidene)methyl) (4-methoxystyryl) sulfide (BMMS) by using the forced swimming test (FST) and the tail suspension test (TST) in Swiss mice. The contribution of serotoninergic, glutamatergic and nitrergic systems in the antidepressant-like activity of BMMS was evaluated. We also examined the involvement of monoamine oxidase (MAO)-A, MAO-B and Na+, K+-ATPase activities in prefrontal cortex of mice. BMMS, (0.1–10 mg/kg, intragastrically (i.g.)) and fluoxetine (32 mg/kg, i.g.) decreased the immobility time in the FST and TST. The anti-immobility effect of BMMS (10 mg/kg, i.g.) in the TST was prevented by the pretreatment of mice with WAY100635 (0.1 mg/kg, subcutaneously (s.c.), a 5-HT1A receptor antagonist), ketanserin (5 mg/kg, intraperitoneal (i.p.), a 5-HT2A/2C receptor antagonist), and partially blocked by ondansetron (1 mg/kg, i.p., a 5-HT3 receptor antagonist). The anti-immobility effect of BMMS (10 mg / kg, i.g.) was not avoided by pretreatment with MK-801 (0.01 mg/kg, s.c. a non-competitive N-methyl D-Aspartate (NMDA) receptor) in the TST. Pretreatment with L-arginine (500 mg/kg, i.p., a nitric oxide precursor) reversed partially the reduction in the immobility time elicited by BMMS (10 mg/kg, i.g.) in TST. BMMS altered Na+,K+-ATPase and MAO-A activities in prefrontal cortex of mice, but was not able to change the MAO-B activity. In conclusion, BMMS exerted an antidepressant-like effect in mice and serotonergic and nitrergic systems are involved in the antidepressant-like action of compound. BMMS modulated MAO-A and Na+, K+- ATPase activities in prefrontal cortex of mice.


Sulfur Depression Serotonin Nitric oxide Na+ K+-ATPase Monoamine oxidase 



We are grateful for the financial support and scholarships from the Brazilian agencies CNPq (UNIVERSAL 408874/2016-3), FAPERGS (PRONEM 16/2551-0000240-1, PRONUPEQ 16/2551-0000526-5 and PqG 17/2551-0001013-2). CNPq is also acknowledged for the fellowship to C.C.S., E.A.W. and C. L. This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível superior – Brasil (CAPES) - Finance Code 001.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Renata L. de Oliveira
    • 1
  • Guilherme T. Voss
    • 1
  • Jaini J. Paltian
    • 1
  • Mikaela P. Pinz
    • 1
  • Marina Laura C. P. Torres
    • 1
  • Michele P. Moreira
    • 2
  • Marina C. Dilelio
    • 3
  • Claudio C. Silveira
    • 3
  • Ethel A. Wilhelm
    • 1
    Email author
  • Cristiane Luchese
    • 1
    Email author
  1. 1.Programa de Pós-graduação em Bioquímica e Bioprospecção, Laboratório de Pesquisa em Farmacologia Bioquímica (LaFarBio), Grupo de Pesquisa em Neurobiotecnologia (GPN), Centro de Ciências Químicas, Farmacêuticas e de AlimentosUniversidade Federal de PelotasPelotasBrazil
  2. 2.Programa de Pós-Graduação em Nanociências, Centro de Ciências TecnológicasUniversidade FranciscanaSanta MariaBrazil
  3. 3.Departamento de QuímicaUniversidade Federal de Santa MariaSanta MariaBrazil

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