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 schizophrenia are discussed.
Malhotra
A K
AK
Experimental Therapeutics Branch, National Institute of Mental Health, Bethesda, MD 20892, USA.
Pinals
D A
DA
Weingartner
H
H
Sirocco
K
K
Missar
C D
CD
Pickar
D
D
Breier
A
A
D000328:Adult; D003071:Cognition / Q000187:drug effects*; D004311:Double-Blind Method; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007649:Ketamine / Q000494:pharmacology*; D008297:Male; D008568:Memory / Q000187:drug effects*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*
D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D007649:Ketamine