Resveratrol abrogates lipopolysaccharide-induced depressive-like behavior, neuroinflammatory response, and CREB/BDNF signaling in mice

Eur J Pharmacol. 2015 Dec 5:768:49-57. doi: 10.1016/j.ejphar.2015.10.026. Epub 2015 Oct 17.


Current evidence supports that depression is accompanied by the activation of the inflammatory-response system, and overproduction of pro-inflammatory cytokines may play a role in the pathophysiology of depressive disorders. Resveratrol has anti-inflammatory, antioxidant and anti-depressant-like properties. Using an animal model of depression induced by a single administration of lipopolysaccharide (LPS), the present study investigated the effects of resveratrol on LPS-induced depressive-like behavior and inflammatory-response in adult mice. Our results showed that pretreatment with resveratrol (80mg/kg, i.p.) for 7 consecutive days reversed LPS-increased the immobility time in the forced swimming test and tail suspension test, and LPS-reduced sucrose preference test. Moreover, the antidepressant action of resveratrol was paralleled by significantly reducing the expression levels of pro-inflammatory cytokines, and up-regulating phosphorylated cAMP response-element-binding protein (pCREB)/brain-derived neurotrophic factor (BDNF) expression in prefrontal cortex (PFC) and hippocampus. In addition, resveratrol ameliorated LPS-induced NF-κB activation in the PFC and hippocampus. The results demonstrate that resveratrol may be an effective therapeutic agent for LPS-induced depressive-like behavior, partially due to its anti-inflammatory aptitude and by modulating pCREB and BDNF expression in the brain region of mice.

Keywords: Depression; Lipopolysaccharide; NF-κB; Pro-inflammatory cytokines; Resveratrol.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antidepressive Agents / pharmacology
  • Antidepressive Agents / therapeutic use
  • Behavior, Animal / drug effects*
  • Brain / drug effects*
  • Brain / pathology
  • Brain-Derived Neurotrophic Factor / metabolism*
  • Cell Nucleus / drug effects
  • Cell Nucleus / metabolism
  • Cyclic AMP / metabolism
  • Cyclic AMP Response Element-Binding Protein / metabolism*
  • Cytokines / metabolism
  • Depression / drug therapy*
  • Depression / metabolism
  • Depression / pathology
  • Food Preferences / drug effects
  • Hippocampus / pathology
  • Inflammation / drug therapy
  • Lipopolysaccharides / pharmacology*
  • Male
  • Mice
  • Motor Activity / drug effects
  • NF-kappa B / metabolism
  • Prefrontal Cortex / pathology
  • Resveratrol
  • Signal Transduction / drug effects
  • Stilbenes / pharmacology*
  • Stilbenes / therapeutic use
  • Sucrose / pharmacology


  • Antidepressive Agents
  • Brain-Derived Neurotrophic Factor
  • Cyclic AMP Response Element-Binding Protein
  • Cytokines
  • Lipopolysaccharides
  • NF-kappa B
  • Stilbenes
  • Sucrose
  • Cyclic AMP
  • Resveratrol