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.