Quercetin protects the impairment of memory and anxiogenic-like behavior in rats exposed to cadmium: Possible involvement of the acetylcholinesterase and Na(+),K(+)-ATPase activities

Physiol Behav. 2014 Aug;135:152-67. doi: 10.1016/j.physbeh.2014.06.008. Epub 2014 Jun 18.


The present study investigated the effects of quercetin in the impairment of memory and anxiogenic-like behavior induced by cadmium (Cd) exposure. We also investigated possible alterations in acetylcholinesterase (AChE), Na(+),K(+)-ATPase and δ-aminolevulinate dehydratase (δ-ALA-D) activities as well as in oxidative stress parameters in the CNS. Rats were exposed to Cd (2.5mg/kg) and quercetin (5, 25 or 50mg/kg) by gavage for 45days. Animals were divided into eight groups (n=10-14): saline/control, saline/Querc 5mg/kg, saline/Querc 25mg/kg, saline/Querc 50mg/kg, Cd/ethanol, Cd/Querc 5mg/kg, Cd/Querc 25mg/kg and Cd/Querc 50mg/kg. Results demonstrated that Cd impaired memory has an anxiogenic effect. Quercetin prevented these harmful effects induced by Cd. AChE activity decreased in the cerebral cortex and hippocampus and increased in the hypothalamus of Cd-exposed rats. The Na(+),K(+)-ATPase activity decreased in the cerebral cortex, hippocampus and hypothalamus of Cd-exposed rats. Quercetin prevented these effects in AChE and Na(+),K(+)-ATPase activities. Reactive oxygen species production, thiobarbituric acid reactive substance levels, protein carbonyl content and double-stranded DNA fractions increased in the cerebral cortex, hippocampus and hypothalamus of Cd-exposed rats. Quercetin totally or partially prevents these effects caused by Cd. Total thiols (T-SHs), reduced glutathione (GSH), and reductase glutathione (GR) activities decreased and glutathione S-transferase (GST) activity increased in Cd exposed rats. Co-treatment with quercetin prevented reduction in T-SH, GSH, and GR activities and the rise of GST activity. The present findings show that quercetin prevents alterations in oxidative stress parameters as well as AChE and Na(+),K(+)-ATPase activities, consequently preventing memory impairment and anxiogenic-like behavior displayed by Cd exposure. These results may contribute to a better understanding of the neuroprotective role of quercetin, emphasizing the influence of this flavonoid in the diet for human health, possibly preventing brain injury associated with Cd intoxication.

Keywords: AChE; Anxiety; Cd; K(+)-ATPase; Memory; Na(+); Oxidative stress; Quercetin.

MeSH terms

  • Acetylcholinesterase / metabolism*
  • Animals
  • Anxiety / chemically induced
  • Anxiety / enzymology
  • Anxiety / prevention & control*
  • Behavior, Animal / drug effects
  • Cadmium / toxicity*
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / enzymology
  • Hippocampus / drug effects
  • Hippocampus / enzymology
  • Male
  • Memory / drug effects
  • Memory Disorders / chemically induced
  • Memory Disorders / enzymology
  • Memory Disorders / prevention & control*
  • Neuroprotective Agents / pharmacology
  • Neuroprotective Agents / therapeutic use
  • Oxidative Stress / drug effects
  • Porphobilinogen Synthase / metabolism
  • Quercetin / pharmacology*
  • Quercetin / therapeutic use
  • Rats
  • Rats, Wistar
  • Reactive Oxygen Species / metabolism
  • Sodium-Potassium-Exchanging ATPase / metabolism*


  • Neuroprotective Agents
  • Reactive Oxygen Species
  • Cadmium
  • Quercetin
  • Acetylcholinesterase
  • Porphobilinogen Synthase
  • Sodium-Potassium-Exchanging ATPase