Cited by 1,020Schizophrenia research and treatmentNeuroscience and Neuropharmacology ResearchNeurotransmitter Receptor Influence on Behavior

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NMDA receptor hypofunction model of schizophrenia

Olney, John W, Newcomer, John W, Farber, Nuri B·1999·Journal of Psychiatric Research

DOI 10.1016/s0022-3956(99)00029-1

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Abstract

Several decades of research attempting to explain schizophrenia in terms of the dopamine hyperactivity hypothesis have produced disappointing results. A new hypothesis focusing on hypofunction of the NMDA glutamate transmitter system is emerging as a potentially more promising concept. In this article, we present a version of the NMDA receptor hypofunction hypothesis that has evolved from our recent studies pertaining to the neurotoxic and psychotomimetic effects of PCP and related NMDA antagonist drugs. In this article, we examine this hypothesis in terms of its strengths and weaknesses, its therapeutic implications and ways in which it can be further tested.

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Authors: Olney, J. W., Newcomer, J. W., & Farber, N. B.
Affiliations: Washington University in St. Louis (US)
Corresponding author: Olney, John W
ORCID: Newcomer, John W
Farber, Nuri B
Venue: Journal of Psychiatric Research
Publisher: Elsevier BV
Published: 1999-11
Volume: 33
Issue: 6
Pages: 523-533
ISSN: 0022-3956 (ISSN-L)
DOI: 10.1016/s0022-3956(99)00029-1
OpenAlex: W2084120702
Cited by: 1,020
References: 63
Citations by year: 2026: 15 · 2025: 17 · 2024: 25 · 2023: 23 · 2022: 24 · 2021: 30 · 2020: 32 · 2019: 33 · 2018: 28 · 2017: 46 · 2016: 29 · 2015: 50 · 2014: 56 · 2013: 38 · 2012: 55
FWCI: 11.92
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Journal of Psychiatric Research (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (5k02mh001510-05, 5k20da000290-05)
National Institute of Mental Health (MH33894, MH-01510)
National Institute on Drug Abuse (DA00290)
Topics: Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Keywords: schizophrenia, NMDA receptor hypofunction, phencyclidine, NMDA receptor antagonists, neurotoxicity, psychotomimetic effects, schizophrenia treatment
MeSH terms: Animals, Disease Models, Animal, Enzyme Inhibitors, Humans, Models, Biological, Models, Psychological, Phencyclidine, Schizophrenia, Receptors, N-Methyl-D-Aspartate, Rats

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