Quercetin reduces manic-like behavior and brain oxidative stress induced by paradoxical sleep deprivation in mice

Free Radic Biol Med. 2016 Oct:99:79-86. doi: 10.1016/j.freeradbiomed.2016.07.027. Epub 2016 Jul 28.

Abstract

Quercetin is a known antioxidant and protein kinase C (PKC) inhibitor. Previous studies have shown that mania involves oxidative stress and an increase in PKC activity. We hypothesized that quercetin affects manic symptoms. In the present study, manic-like behavior (hyperlocomotion) and oxidative stress were induced by 24h paradoxical sleep deprivation (PSD) in male Swiss mice. Both 10 and 40mg/kg quercetin prevented PSD-induced hyperlocomotion. Quercetin reversed the PSD-induced decrease in glutathione (GSH) levels in the prefrontal cortex (PFC) and striatum. Quercetin also reversed the PSD-induced increase in lipid peroxidation (LPO) in the PFC, hippocampus, and striatum. Pearson's correlation analysis revealed a negative correlation between locomotor activity and GSH in the PFC in sleep-deprived mice and a positive correlation between locomotor activity and LPO in the PFC and striatum in sleep-deprived mice. These results suggest that quercetin exerts an antimanic-like effect at doses that do not impair spontaneous locomotor activity, and the antioxidant action of quercetin might contribute to its antimanic-like effects.

Keywords: Bipolar disorder; Mania; Oxidative stress; Paradoxical sleep deprivation; Protein kinase C; Quercetin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antimanic Agents / pharmacology*
  • Antioxidants / pharmacology*
  • Bipolar Disorder / drug therapy*
  • Bipolar Disorder / etiology
  • Bipolar Disorder / metabolism
  • Bipolar Disorder / physiopathology
  • Corpus Striatum / drug effects
  • Corpus Striatum / metabolism
  • Disease Models, Animal
  • Drug Administration Schedule
  • Glutathione / agonists
  • Glutathione / metabolism
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Lipid Peroxidation / drug effects
  • Male
  • Mice
  • Oxidative Stress / drug effects*
  • Prefrontal Cortex / drug effects
  • Prefrontal Cortex / metabolism
  • Psychomotor Agitation / drug therapy*
  • Psychomotor Agitation / etiology
  • Psychomotor Agitation / metabolism
  • Psychomotor Agitation / physiopathology
  • Quercetin / pharmacology*
  • Sleep Deprivation / complications
  • Sleep Deprivation / metabolism
  • Sleep Deprivation / physiopathology

Substances

  • Antimanic Agents
  • Antioxidants
  • Quercetin
  • Glutathione