Antidepressant-like activity of resveratrol treatment in the forced swim test and tail suspension test in mice: the HPA axis, BDNF expression and phosphorylation of ERK

Pharmacol Biochem Behav. 2013 Nov:112:104-10. doi: 10.1016/j.pbb.2013.10.007. Epub 2013 Oct 11.


Resveratrol is a natural polyphenol enriched in Polygonum cuspidatum and has diverse biological activities. There is only limited information about the antidepressant-like effect of resveratrol. The present study assessed whether resveratrol treatment (20, 40 and 80mg/kg, i.p., 21days) has an antidepressant-like effect on the forced swim test (FST) and tail suspension test (TST) in mice and examined what its molecular targets might be. The results showed that resveratrol administration produced antidepressant-like effects in mice, evidenced by the reduced immobility time in the FST and TST, while it had no effect on the locomotor activity in the open field test. Resveratrol treatment significantly reduced serum corticosterone levels, which had been elevated by the FST and TST. Moreover, resveratrol increased brain-derived neurotrophic factor (BDNF) protein and extracellular signal-regulated kinase (ERK) phosphorylation levels in the prefrontal cortex and hippocampus. All of these antidepressant-like effects of resveratrol were essentially similar to those observed with the clinical antidepressant, fluoxetine. These results suggest that the antidepressant-like effects of resveratrol in the FST and TST are mediated, at least in part, by modulating hypothalamic-pituitary-adrenal axis, BDNF and ERK phosphorylation expression in the brain region of mice.

Keywords: BDNF; Brain derived neurotrophic factor (BDNF); ERK; Extracellular signal-regulated kinase (ERK); FST; Forced swim test; HPA; PFC; RT-PCR; Resveratrol; TST; Tail suspension test; The hypothalamic–pituitary–adrenal axis; brain derived neurotrophic factor; extracellular signal-regulated kinase; forced swim test; hypothalamic–pituitary–adrenal; prefrontal cortex; reverse transcription-polymerase chain reaction; tail suspension test.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antidepressive Agents / pharmacology*
  • Brain-Derived Neurotrophic Factor / metabolism*
  • Extracellular Signal-Regulated MAP Kinases / metabolism*
  • Hindlimb Suspension
  • Hypothalamo-Hypophyseal System*
  • Male
  • Mice
  • Phosphorylation
  • Pituitary-Adrenal System*
  • Resveratrol
  • Stilbenes / pharmacology*
  • Stress, Physiological*
  • Swimming


  • Antidepressive Agents
  • Brain-Derived Neurotrophic Factor
  • Stilbenes
  • Extracellular Signal-Regulated MAP Kinases
  • Resveratrol