Behavioral alterations and pro-oxidant effect of a single ketamine administration to mice

Brain Res Bull. 2010 Aug 30;83(1-2):9-15. doi: 10.1016/j.brainresbull.2010.05.011. Epub 2010 Jul 1.

Abstract

A growing body of evidence has pointed to the ionotropic glutamate N-methyl-d-aspartate receptor (NMDA) as an important player in the etiology of psychopathologies, including anxiety and major depression. Clinical findings suggest that ketamine may be used for the treatment of major depression. There is evidence that reactive oxygen species also play an important role in the pathogenesis of many diseases, particularly those which are neurological and psychiatric in nature. This study examined the behavioral and oxidative stress alterations after a single administration of ketamine (5, 10 and 20mg/kg i.p.) in mice. Ketamine presented a significant anxiogenic effect in the elevated plus-maze model of anxiety, also increasing locomotor activity. In the forced swimming and tail suspension tests, a significant decrease in immobility time after ketamine administration was observed. In addition to the behavioral changes induced by ketamine, this drug also increased lipid peroxidation, nitrite content and catalase activity, while decreased GSH levels in mice prefrontal cortex. In conclusion, our results confirm the antidepressant effects of ketamine, also showing a pro-oxidant effect of this drug.

MeSH terms

  • Analysis of Variance
  • Animals
  • Behavior, Animal / drug effects*
  • Catalase / metabolism
  • Dose-Response Relationship, Drug
  • Excitatory Amino Acid Antagonists / pharmacology*
  • Exploratory Behavior / drug effects
  • Glutathione / metabolism
  • Hindlimb Suspension / methods
  • Ketamine / pharmacology*
  • Lipid Peroxidation / drug effects
  • Male
  • Maze Learning / drug effects
  • Mice
  • Nitrites / metabolism
  • Oxidative Stress / drug effects*
  • Oxidative Stress / physiology
  • Prefrontal Cortex / drug effects
  • Prefrontal Cortex / metabolism
  • Swimming / psychology
  • Thiobarbituric Acid Reactive Substances / metabolism

Substances

  • Excitatory Amino Acid Antagonists
  • Nitrites
  • Thiobarbituric Acid Reactive Substances
  • Ketamine
  • Catalase
  • Glutathione