Effects of the NMDA antagonist ketamine on task-switching performance: evidence for specific impairments of executive control

Neuropsychopharmacology. 2006 Aug;31(8):1675-81. doi: 10.1038/sj.npp.1300930. Epub 2005 Oct 5.

Abstract

In humans, the effects of subanesthetic doses of ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, substantially impair executive control functions. Here, we consider whether ketamine exposure can provide an animal model for the effects of ketamine on executive control. Two monkeys (Macaca mulatta) performed a cued task-switching paradigm. We studied their behavior before and after a range of ketamine doses. We found that ketamine slowed overall performance and decreased overall accuracy, strongly impaired the capacity to ignore task-irrelevant information and, to a lesser degree, decreased accuracy when a task switch was required. This pattern of results is very similar to that found in studies of schizophrenic patients performing task-switching paradigms or the Stroop task. We conclude that ketamine in monkeys provides a good animal model for exploring the relationship between the glutamate system, executive control, and the symptoms of schizophrenia.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dose-Response Relationship, Drug
  • Excitatory Amino Acid Antagonists / pharmacology*
  • Ketamine / pharmacology*
  • Macaca mulatta
  • Male
  • Psychomotor Performance / drug effects*
  • Psychomotor Performance / physiology
  • Reaction Time / drug effects
  • Reaction Time / physiology
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors*
  • Receptors, N-Methyl-D-Aspartate / physiology
  • Schizophrenia / physiopathology

Substances

  • Excitatory Amino Acid Antagonists
  • Receptors, N-Methyl-D-Aspartate
  • Ketamine