NMDA Receptor Function and Human Cognition: The Effects of Ketamine in Healthy Volunteers


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 schizophremia are discussed.

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Correspondence to Anil K Malhotra MD.

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Malhotra, A., Pinals, D., Weingartner, H. et al. NMDA Receptor Function and Human Cognition: The Effects of Ketamine in Healthy Volunteers. Neuropsychopharmacol 14, 301–307 (1996). https://doi.org/10.1016/0893-133X(95)00137-3

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

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