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Mice with Reduced NMDA Receptor Expression Display Behaviors Related to Schizophrenia
Open accessAbstract
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 (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
In the citing paper
“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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Metadata
- 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
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 1999-08
- Volume
- 98
- Issue
- 4
- Pages
- 427-436
- ISSN
- 0092-8674 (ISSN-L)
- 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
- 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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