Cited by 157Schizophrenia research and treatmentNeurotransmitter Receptor Influence on BehaviorNeuroscience and Neuropharmacology Research

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Transient N-methyl-D-aspartate receptor blockade in early development causes lasting cognitive deficits relevant to schizophrenia

Stefani, Mark Renato, Moghaddam, Bita·2005·Biological Psychiatry

DOI 10.1016/j.biopsych.2004.11.031

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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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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)
DOI: 10.1016/j.biopsych.2004.11.031
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
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
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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Transient N-methyl-D-aspartate receptor blockade in early development causes lasting cognitive deficits relevant to schizophrenia

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