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

Mark Renato Stefani, Bita Moghaddam

Research output: Contribution to journalArticlepeer-review

128 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)433-436
Number of pages4
JournalBiological Psychiatry
Volume57
Issue number4
DOIs
StatePublished - Feb 15 2005

Keywords

  • Glutamate
  • MK801
  • Memory
  • Prefrontal
  • Set-shift
  • Spontaneous alternation

ASJC Scopus subject areas

  • Biological Psychiatry

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