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Updated: Aug 19, 2026

Immunohistochemical Visualization of Hippocampal Neuron Activity After Spatial Learning in a Mouse Model of Neurodevelopmental Disorders
Published on: May 12, 2015
Transient N-methyl-D-aspartate receptor blockade in early development causes lasting cognitive deficits relevant to
Mark Renato Stefani1, Bita Moghaddam
1Department of Neuroscience, University of Pittsburgh, Pittsburgh, Pennsylvania, USA. stefani@bns.pitt.edu
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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