NMDA receptor function and human cognition: The effects of ketamine in healthy volunteers

Anil K. Malhotra, Debra A. Pinals, Herbert Weingartner, Karen Sirocco, C. David Missar, David Pickar, Alan Breier

Research output: Contribution to journalArticlepeer-review

526 Scopus citations


A rapidly growing body of preclinical data has implicated the glutamatergic N-methyl-d-aspartate (NMDA) receptor in memory and other cognitive processes. There is comparatively less information about this receptor system in human cognition. We examined the effects of subanesthetic doses of ketamine, a noncompetitive NMDA receptor antagonist, on two forms of memory, free recall and recognition, as well as attention and behavior in a double-blind, placebo-controlled, 1-hour infusion in 15 healthy volunteers. Ketamine produced decrements in free recall, recognition memory, and attention. In addition, ketamine induced a brief psychosis in our healthy volunteers marked by thought disorder and withdrawal-retardation. Ketamine-induced memory impairments were not accounted for by changes in subject's attention and were not significantly related to psychosis ratings. These data suggest that the NMDA receptor plays a direct role in two types of explicit memory. The implications of these data for the pathophysiology of schizophrenia are discussed.

Original languageEnglish (US)
Pages (from-to)301-307
Number of pages7
Issue number5
StatePublished - May 1996
Externally publishedYes


  • Cognition
  • Ketamine
  • Memory
  • Psychotic disorders
  • Receptors, glutamate
  • Receptors, N-methyl-d-aspartate

ASJC Scopus subject areas

  • Pharmacology


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