The DOI matches its Crossref record; 31 of the 32 references it cites were found in a registry or an index.
Transient N-methyl-D-aspartate receptor blockade in early development causes lasting cognitive deficits relevant to schizophrenia
Abstract
Background Aberrant N-methyl-D-aspartate (NMDA) receptor-mediated glutamatergic transmission has been implicated in schizophrenia. We studied whether transient inhibition of NMDA receptor activity during early postnatal development would produce a behavioral phenotype resembling that of individuals who are susceptible to develop schizophrenia.Methods Rat pups were given injections of the NMDA channel blocker MK801 on postnatal days 7 through 10. This period is akin to the prenatal second trimester of primate development. Cognitive function was tested in adulthood.Results Treatment with MK801 impaired cognitive flexibility and working memory. The impairment in cognitive flexibility was due to increased perseverative behavior. Treatment did not affect locomotor activity or recognition memory.Conclusions These results suggest that a brief disruption of NMDA receptors during a sensitive period of cortical development is sufficient to produce selective cognitive deficits that are relevant to schizophrenia.
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“A milder antagonism regime caused long-lasting behavioural changes and a specific longlasting decrease in cortical PVI numbers 29 , mimicking a key pathological feature of schizophrenia 2 .”
From Linking early-life NMDAR hypofunction and oxidative stress in schizophrenia pathogenesis (2016) · cites this paper as [29]
In the citing paper
“NMDAR antagonism likely induces a hyperglutamatergic state by reducing the activity of cortical interneurons, which particularly rely on NMDARs for their excitatory drive early in development 29,79 .”
From Linking early-life NMDAR hypofunction and oxidative stress in schizophrenia pathogenesis (2016) · cites this paper as [29]
In the citing paper
“Moreover, and as a result, PVI function itself might be permanently impaired as a result of relatively mild transient NMDAR hypofunction in the developing mouse that does not induce neuronal death 29,80 .”
From Linking early-life NMDAR hypofunction and oxidative stress in schizophrenia pathogenesis (2016) · cites this paper as [29]
In the citing paper
“The mechanism underlying this proposed loss of PVI phenotype involves cortical disinhibition leading to neuronal IL-6 production and consequent activation of NADPH oxidase, which generates H 2 O 2 29 .”
From Linking early-life NMDAR hypofunction and oxidative stress in schizophrenia pathogenesis (2016) · cites this paper as [29]
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Metadata
- Authors
- Stefani, M. R., & Moghaddam, B.
- Affiliations
- University of Pittsburgh (US)
- Corresponding author
- Stefani, Mark Renato
- ORCID
- Moghaddam, Bita
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2005-02
- Volume
- 57
- Issue
- 4
- Pages
- 433-436
- ISSN
- 0006-3223 (ISSN-L)
- OpenAlex
- W1983202833
- Cited by
- 157
- References
- 32
- Citations by year
- 2026: 6 · 2025: 1 · 2024: 2 · 2023: 2 · 2022: 2 · 2021: 7 · 2020: 2 · 2019: 13 · 2018: 3 · 2017: 6 · 2016: 4 · 2015: 12 · 2014: 9 · 2013: 15 · 2012: 16
- FWCI
- 5.41
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Mental Health (R21 MH65026, K02 MH01616, K02MH001616, R37MH048404, R37-MH48404, R21MH065026)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- NMDA receptor, MK-801, schizophrenia, cognitive flexibility, working memory, perseveration, glutamatergic neurotransmission, postnatal development, cortical development, cognitive impairment, rat model
- MeSH terms
- Age Factors, Animals, Animals, Newborn, Behavior, Animal, Cognition Disorders, Discrimination, Psychological, Exploratory Behavior, Locomotion, Male, Memory, Short-Term, Neuropsychological Tests, Psychomotor Performance, Schizophrenia, Receptors, N-Methyl-D-Aspartate, Dizocilpine Maleate, Rats, Sprague-Dawley, Rats
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