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)

Metab Brain Dis. 2019 Oct;34(5):1313-1324. doi: 10.1007/s11011-019-00436-x. Epub 2019 Jun 8.

Abstract

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.

Keywords: Depression; K+-ATPase; Monoamine oxidase; Na+; Nitric oxide; Serotonin; Sulfur.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antidepressive Agents / pharmacology*
  • Antidepressive Agents / therapeutic use
  • Arginine / pharmacology
  • Behavior, Animal / drug effects
  • Depression / drug therapy*
  • Depression / metabolism
  • Disease Models, Animal
  • Excitatory Amino Acid Antagonists / pharmacology
  • Fluoxetine / pharmacology
  • Fluoxetine / therapeutic use
  • Hindlimb Suspension
  • Male
  • Mice
  • Monoamine Oxidase / metabolism
  • Motor Activity / drug effects
  • Nitric Oxide / metabolism*
  • Prefrontal Cortex / drug effects
  • Prefrontal Cortex / metabolism
  • Serotonin / metabolism*
  • Serotonin Antagonists / pharmacology
  • Sodium-Potassium-Exchanging ATPase / metabolism
  • Styrenes / pharmacology*
  • Styrenes / therapeutic use
  • Sulfides / pharmacology*
  • Sulfides / therapeutic use

Substances

  • ((4-tert-butylcyclohexylidene)methyl) (4-methoxystyryl) sulfide
  • Antidepressive Agents
  • Excitatory Amino Acid Antagonists
  • Serotonin Antagonists
  • Styrenes
  • Sulfides
  • Fluoxetine
  • Nitric Oxide
  • Serotonin
  • Arginine
  • Monoamine Oxidase
  • Sodium-Potassium-Exchanging ATPase