The memory stages of a spatial Y-maze task are not affected by a low dose of ketamine/midazolam

Eur J Pharmacol. 2013 Jul 15;712(1-3):39-47. doi: 10.1016/j.ejphar.2013.04.027. Epub 2013 May 9.


Anesthetics, such as the ketamine/midazolam combination, are used in research with animals and in human clinical practice; thus, it is essential to clarify the potential effects of these anesthetics on memory. This study aimed to evaluate how a low dose of the ketamine/midazolam combination affects the acquisition, consolidation, or recall of a spatial memory task. Thirty-three adult male C57BL/6 mice were divided into four treatment groups: unanesthetized control animals and three groups of animals treated with 40 mg/kg of ketamine and 10mg/kg of midazolam administered in a single intraperitoneal injection. The different treatment groups received the same anesthetic dose at different time points, to study the acquisition, consolidation, and recall of spatial memory in the Y-maze task. The percentage of correct choices was measured. Six mice were killed 4 days and 12 days after anesthesia for histopathological analyses. There were no differences between treatment and control groups regarding the acquisition of spatial memory, measured as the slope of the learning curve, or in the percentage of correct choices in the consolidation or recall periods of the task. Similarly, no differences were detected between groups regarding the number of cells per square millimeter in the visual and retrosplenial cortex, in the dentate gyrus, and in the CA1 and CA3 regions of the hippocampus. Hence, a low dose of the ketamine/midazolam combination did not impair memory processes or brain integrity in adult mice, suggesting that this combination is unlikely to cause cognitive complications.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anesthetics / pharmacology*
  • Animals
  • Brain / cytology
  • Brain / drug effects
  • Brain / physiology
  • Choice Behavior / drug effects
  • Choice Behavior / physiology
  • Dose-Response Relationship, Drug
  • Ketamine / pharmacology*
  • Male
  • Maze Learning / drug effects*
  • Maze Learning / physiology*
  • Memory / drug effects*
  • Mice
  • Mice, Inbred C57BL
  • Midazolam / pharmacology*
  • Spatial Behavior / drug effects
  • Spatial Behavior / physiology*


  • Anesthetics
  • Ketamine
  • Midazolam