Cited by 1,075Schizophrenia research and treatmentNeuroscience and Neuropharmacology ResearchNeurotransmitter Receptor Influence on Behavior

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Mice with Reduced NMDA Receptor Expression Display Behaviors Related to Schizophrenia

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Mohn, Amy R, Gainetdinov, Raul R, Caron, Marc G, Koller, Beverly H·1999·Cell

DOI 10.1016/s0092-8674(00)81972-8

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Abstract

N-methyl-D-aspartate receptors (NMDARs) represent a subclass of glutamate receptors that play a critical role in neuronal development and physiology. We report here the generation of mice expressing only 5% of normal levels of the essential NMDAR1 (NR1) subunit. Unlike NR1 null mice, these mice survive to adulthood and display behavioral abnormalities, including increased motor activity and stereotypy and deficits in social and sexual interactions. These behavioral alterations are similar to those observed in pharmacologically induced animal models of schizophrenia and can be ameliorated by treatment with haloperidol or clozapine, antipsychotic drugs that antagonize dopaminergic and serotonergic receptors. These findings support a model in which reduced NMDA receptor activity results in schizophrenic-like behavior and reveals how pharmacological manipulation of monoaminergic pathways can affect this phenotype.

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Authors: Mohn, A. R., Gainetdinov, R. R., Caron, M. G., & Koller, B. H.
Affiliations: University of North Carolina at Chapel Hill (US)
Howard Hughes Medical Institute (US)
Corresponding author: Koller, Beverly H
ORCID: Gainetdinov, Raul R
Caron, Marc G
Koller, Beverly H
Venue: Cell
Publisher: Elsevier BV
Published: 1999-08
Volume: 98
Issue: 4
Pages: 427-436
ISSN: 0092-8674 (ISSN-L)
DOI: 10.1016/s0092-8674(00)81972-8
OpenAlex: W2164674870
Cited by: 1,075
References: 64
Citations by year: 2026: 13 · 2025: 14 · 2024: 19 · 2023: 17 · 2022: 28 · 2021: 26 · 2020: 26 · 2019: 28 · 2018: 29 · 2017: 27 · 2016: 46 · 2015: 40 · 2014: 39 · 2013: 42 · 2012: 45
FWCI: 24.23
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 5099 d)
Locations: Cell (publishedVersion)
PubMed (publishedVersion)
Funders: National Institute of General Medical Sciences (T32GM007092, T32 GM07092)
National Institute of Neurological Disorders and Stroke (NS-19576, R01NS019576)
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: NMDA receptor, NR1 subunit, schizophrenia, mouse model, motor activity, stereotypy, social interaction deficits, antipsychotic drugs, haloperidol, clozapine, monoaminergic pathways, glutamate receptors
MeSH terms: Animals, Antisocial Personality Disorder, Behavior, Animal, Clozapine, Disease Models, Animal, Female, Haloperidol, Male, Motor Activity, Phencyclidine, Schizophrenic Psychology, Serotonin Antagonists, Sexual Behavior, Animal, Social Behavior, Stereotyped Behavior, Antipsychotic Agents, Receptors, N-Methyl-D-Aspartate, Dizocilpine Maleate, Mice, Knockout, Dopamine Antagonists, Excitatory Amino Acid Antagonists, Glutamic Acid, Calcium Signaling, Mice

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Mice with Reduced NMDA Receptor Expression Display Behaviors Related to Schizophrenia

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