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

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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  • Observational findings in some of these behavioral domains have been reported in some targeted gene mutations, e.g. deficits in social interaction within the home cage have been reported for mice deficient in the dishevelled-1 gene or the NMDA NR1 subunit.

    “Observational findings in some of these behavioral domains have been reported in some targeted gene mutations, e.g.deficits in social interaction within the home cage have been reported for mice deficient in the dishevelled-1 gene (Lijam et al. 1997) or the NMDA NR1 subunit (Mohn et al. 1999).”

    From Sociability and preference for social novelty in five inbred strains: an approach to assess autistic‐like behavior in mice (2004) · cites this paper as Mohn et al. 1999

  • NMDAR antagonism during the first 2 postnatal weeks in rodents induces long-lasting behavioural and cognitive disturbances relevant to the schizophrenia phenotype that extend into adolescence and adulthood.

    “In supporting of this notion, NMDAR antagonism during an equivalent period in rodents (first 2 post-natal weeks) induces long-lasting behavioural and cognitive disturbances that are relevant to the schizophrenia phenotype and which extend into adolescence and adulthood 10,27 .”

    From Linking early-life NMDAR hypofunction and oxidative stress in schizophrenia pathogenesis (2016) · cites this paper as [27]

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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
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
Licence
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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