Effects of the cognition impairer MK-801 on learning and memory in mice and rats

Behav Brain Res. 2011 Jun 20;220(1):215-29. doi: 10.1016/j.bbr.2011.01.052. Epub 2011 Feb 15.


There is a great need for relevant animal models for investigating the effects of putative pro-cognitive compounds. Compounds that impair learning and/or memory processes without inducing adverse side effects are cognition impairers. Rats and mice with cognitive deficits induced by the prototypical N-methyl-d-aspartate (NMDA) receptor antagonist MK-801 may provide a relevant animal model based on the mechanistic approach of blocking NMDA/glutamatergic signaling. Unfortunately, the dose range over which MK-801 induces cognitive impairment without causing sensory, locomotor, or toxicological side effects is small. We provide an overview of the effects of MK-801 in different cognitive tasks and assessed whether MK-801 reliably affects the cognitive performance of mice or rats in the spatial Morris task, T-maze alternation tasks, and non-spatial passive avoidance, social, and object recognition tasks. MK-801 disrupted or retarded memory acquisition in all tasks. The Morris task, once acquired, was insensitive to MK-801 at a dose up to 0.1 mg kg(-1) body weight. Retention deficits in the passive avoidance tests were not likely to be due to MK-801-induced changes in shock sensitivity, as measured by a shock threshold test. On the basis of published evidence and the present findings, we conclude that MK-801, administered s.c. or i.p. into rodents in doses up to 0.1 mg kg(-1), appears to fulfill the criteria of our definition of a cognition impairer in rodents, without causing sensorimotor impairments and/or signs of intoxication. In addition, MK-801-treated rodents appear to fulfill the criteria of a valid animal model of cognitive dysfunctions, with robust effects across species, housing conditions, and testing paradigms.

MeSH terms

  • Analysis of Variance
  • Animals
  • Attention / drug effects
  • Avoidance Learning / drug effects*
  • Behavior, Animal / drug effects
  • Dizocilpine Maleate / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Administration Routes
  • Excitatory Amino Acid Antagonists / pharmacology*
  • Male
  • Maze Learning / drug effects*
  • Mice
  • Mice, Inbred C57BL
  • Rats
  • Rats, Wistar
  • Recognition, Psychology / drug effects*
  • Sensory Thresholds / drug effects


  • Excitatory Amino Acid Antagonists
  • Dizocilpine Maleate