Antidepressant-like effect of trans-resveratrol in chronic stress model: behavioral and neurochemical evidences

J Psychiatr Res. 2013 Mar;47(3):315-22. doi: 10.1016/j.jpsychires.2012.10.018. Epub 2012 Nov 19.


Trans-resveratrol is a phenolic compound enriched in polygonum cuspidatum and has diverse biological activities. There is only limited information about the antidepressant-like effect of trans-resveratrol. The present study investigated whether trans-resveratrol has antidepressant-like activity in rats exposed to chronic stress by using two behavioral tasks, shuttle box and sucrose preference tests. The monoamines (5-HT, noradrenaline and dopamine) and their metabolites as well as monoamine oxidase (MAO) enzyme activities in different brain regions were also measured. Compared to unstressed rats, those exposed to chronic stress paradigm showed performance deficits in the shuttle box, reduced sucrose preference, less weight gain and the increase in the ratio of adrenal gland to body weight, which were reversed by chronic treatment with trans-resveratrol (40 and 80 mg/kg, i.g.). The neurochemical assay showed that higher dose of trans-resveratrol (80 mg/kg) produced a marked increase of 5-HT levels in three brain regions, the frontal cortex, hippocampus and hypothalamus. Noradrenaline and dopamine levels were also increased both in the frontal cortex and striatum. Furthermore, chronic treatment with trans-resveratrol was found to inhibit monoamine oxidase-A (MAO-A) activity in all the four brain regions, particularly in the frontal cortex and hippocampus; while MAO-B activity was not affected. These findings indicate that the antidepressant-like effect of trans-resveratrol involves the regulation of the central serotonin and noradrenaline levels and the related MAO-A activities.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Glands / drug effects
  • Animals
  • Antidepressive Agents / pharmacology
  • Antidepressive Agents / therapeutic use*
  • Body Weight / drug effects
  • Brain / drug effects
  • Brain / metabolism*
  • Brain / pathology
  • Chronic Disease
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Escape Reaction / drug effects
  • Fluoxetine / pharmacology
  • Fluoxetine / therapeutic use
  • Food Preferences / drug effects
  • Gene Expression Regulation / drug effects
  • Imipramine / pharmacology
  • Imipramine / therapeutic use
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Resveratrol
  • Stilbenes / pharmacology
  • Stilbenes / therapeutic use*
  • Stress, Psychological / drug therapy*
  • Stress, Psychological / metabolism
  • Stress, Psychological / pathology
  • Stress, Psychological / physiopathology
  • Sucrose / administration & dosage
  • Sweetening Agents / administration & dosage
  • Time Factors
  • Water Deprivation


  • Antidepressive Agents
  • Stilbenes
  • Sweetening Agents
  • Fluoxetine
  • Sucrose
  • Imipramine
  • Resveratrol