TY - JOUR
T1 - Ketamine-induced NMDA receptor hypofunction as a model of memory impairment and psychosis
AU - Newcomer, John W.
AU - Farber, Nuri B.
AU - Jevtovic-Todorovic, Vesna
AU - Selke, Gregg
AU - Melson, Angela Kelly
AU - Hershey, Tamara
AU - Craft, Suzanne
AU - Olney, John W.
N1 - Funding Information:
Supported by an Independent Scientist Award (MH01510; JWN) from the National Institute of Mental Health (NIMH), MH53363 (JWN), a Scientist Development Award from the National Institute of Drug Abuse (DA00290; NBF), an Established Investigator Award from NARSAD (JWO), a Research Scientist Award from the NIMH (MH38894; JWO), AG11355 (JWO) and U.S.P.H.S. 5M01 RR00036 and P60-DK20579.
PY - 1999/2
Y1 - 1999/2
N2 - N-methyl-D-aspartate (NMDA) glutamate receptor antagonists are reported to induce schizophrenia-like symptoms in humans, including cognitive impairments. Shortcomings of most previous investigations include failure to maintain steady-state infusion conditions, test multiple doses and/or measure antagonist plasma concentrations. This double-blind, placebo-controlled, randomized, within-subjects comparison of three fixed subanesthetic, steady-state doses of intravenous ketamine in healthy males (n = 15) demonstrated dose-dependent increases in Brief Psychiatric Rating Scale positive (F[3,42] = 21.84; p < 0.0001) and negative symptoms (F[3,42] = 2.89; p = 0.047), and Scale for the Assessment of Negative Symptoms (SANS) total scores (F[3,42] = 10.55; p < 0.0001). Ketamine also produced a robust dose-dependent decrease in verbal declarative memory performance (F[3,41] = 5.11; p = 0.004), and preliminary evidence for a similar dose-dependent decrease in nonverbal declarative memory, occurring at or below plasma concentrations producing other symptoms. Increasing NMDA receptor hypofunction is associated with early occurring memory impairments followed by other schizophrenia-like symptoms. Copyright (C) 1999 American College of Neuropsychopharmacology.
AB - N-methyl-D-aspartate (NMDA) glutamate receptor antagonists are reported to induce schizophrenia-like symptoms in humans, including cognitive impairments. Shortcomings of most previous investigations include failure to maintain steady-state infusion conditions, test multiple doses and/or measure antagonist plasma concentrations. This double-blind, placebo-controlled, randomized, within-subjects comparison of three fixed subanesthetic, steady-state doses of intravenous ketamine in healthy males (n = 15) demonstrated dose-dependent increases in Brief Psychiatric Rating Scale positive (F[3,42] = 21.84; p < 0.0001) and negative symptoms (F[3,42] = 2.89; p = 0.047), and Scale for the Assessment of Negative Symptoms (SANS) total scores (F[3,42] = 10.55; p < 0.0001). Ketamine also produced a robust dose-dependent decrease in verbal declarative memory performance (F[3,41] = 5.11; p = 0.004), and preliminary evidence for a similar dose-dependent decrease in nonverbal declarative memory, occurring at or below plasma concentrations producing other symptoms. Increasing NMDA receptor hypofunction is associated with early occurring memory impairments followed by other schizophrenia-like symptoms. Copyright (C) 1999 American College of Neuropsychopharmacology.
KW - Cognition
KW - Glutamate
KW - Ketamine
KW - Memory
KW - NMDA
KW - Schizophrenia
UR - http://www.scopus.com/inward/record.url?scp=0033080733&partnerID=8YFLogxK
U2 - 10.1016/S0893-133X(98)00067-0
DO - 10.1016/S0893-133X(98)00067-0
M3 - Article
C2 - 9885791
AN - SCOPUS:0033080733
SN - 0893-133X
VL - 20
SP - 106
EP - 118
JO - Neuropsychopharmacology
JF - Neuropsychopharmacology
IS - 2
ER -