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

A K Malhotra, D A Pinals, H Weingartner, K Sirocco, C D Missar, D Pickar, A Breier

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology May 1996 DOI: 10.1016/0893-133x(95)00137-3 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Double-blind, placebo-controlled trial Peer reviewed
Sample size 15
Population Healthy volunteers
Intervention Ketamine
Dose subanesthetic doses
Duration 1-hour infusion
Topics Esketamine Ketamine
Key findings Subanesthetic ketamine produced decrements in free recall, recognition memory, and attention in healthy volunteers, and briefly induced psychosis-like symptoms. The memory impairments were not accounted for by attention changes and were not significantly related to psychosis ratings, suggesting the NMDA receptor plays a direct role in explicit memory.

Abstract

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.