Antidepressant-like effect of bis-eugenol in the mice forced swimming test: evidence for the involvement of the monoaminergic system

Fundam Clin Pharmacol. 2013 Oct;27(5):471-82. doi: 10.1111/j.1472-8206.2012.01058.x. Epub 2012 Jul 25.

Abstract

Dehydrodieugenol, known as bis-eugenol, is a eugenol ortho dimer, and both compounds were able to exhibit anti-inflammatory and antioxidant activities in previous studies. Furthermore, eugenol showed antidepressant-like effect; however, the biological actions of bis-eugenol on experimental models for screening antidepressant activity are still unknown. The present study investigated a possible antidepressant-like activity of bis-eugenol in the forced swimming test (FST) and tail suspension test (TST) in mice and the involvement in the monoaminergic system in this effect. In addition, a neurochemical analysis on brain monoamines of mice acutely treated with bis-eugenol was also conducted. Bis-eugenol decreased the immobility time in the FST and TST without accompanying changes in ambulation in the open field test at 10 mg/kg, i.p.. Nevertheless, it induced ambulation at 25 and 50 mg/kg doses. The anti-immobility effect of bis-eugenol (10 and 50 mg/kg, i.p.) was prevented by pretreatment of mice with p-chlorophenylalanine (PCPA, 100 mg/kg, i.p., an inhibitor of serotonin synthesis, for four consecutive days), yohimbine (1 mg/kg, i.p., an α2-adrenoceptor antagonist), SCH23390 (15 μg/kg, s.c., a dopamine D1 receptor antagonist) and sulpiride (50 mg/kg, i.p., a dopamine D2 receptor antagonist). Monoamines analysis using high-performance liquid chromatograph revealed significant increase in the 5-HT, NE and DA levels in brain striatum. The present study indicates that bis-eugenol possesses antidepressant-like activity in FST and TST by altering dopaminergic, serotonergic and noradrenergic systems function.

Keywords: antidepressant-like effect; bis-eugenol; forced swimming test; high-performance liquid chromatography; monoaminergic system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic Neurons / drug effects
  • Adrenergic Neurons / metabolism
  • Animals
  • Antidepressive Agents / administration & dosage
  • Antidepressive Agents / adverse effects
  • Antidepressive Agents / antagonists & inhibitors
  • Antidepressive Agents / therapeutic use*
  • Behavior, Animal / drug effects
  • Biogenic Monoamines / agonists*
  • Biogenic Monoamines / metabolism
  • Corpus Striatum / drug effects*
  • Corpus Striatum / metabolism
  • Depression / drug therapy*
  • Depression / metabolism
  • Disease Models, Animal*
  • Dopamine / chemistry
  • Dopamine / metabolism
  • Dopaminergic Neurons / drug effects
  • Dopaminergic Neurons / metabolism
  • Dose-Response Relationship, Drug
  • Eugenol / administration & dosage
  • Eugenol / adverse effects
  • Eugenol / analogs & derivatives*
  • Eugenol / antagonists & inhibitors
  • Eugenol / therapeutic use
  • Exploratory Behavior / drug effects
  • Lignans / administration & dosage
  • Lignans / adverse effects
  • Lignans / antagonists & inhibitors
  • Lignans / therapeutic use*
  • Male
  • Mice
  • Neurons / drug effects*
  • Neurons / metabolism
  • Norepinephrine / agonists
  • Norepinephrine / metabolism
  • Serotonergic Neurons / drug effects
  • Serotonergic Neurons / metabolism
  • Serotonin / chemistry
  • Serotonin / metabolism
  • Up-Regulation / drug effects

Substances

  • Antidepressive Agents
  • Biogenic Monoamines
  • Lignans
  • dehydrodieugenol
  • Serotonin
  • Eugenol
  • Dopamine
  • Norepinephrine