Effects of neonatal repeated MK-801 treatment on delayed nonmatching-to-position responses in rats

This study was carried out to investigate the long-term effects of chronic neonatal antagonism of N-methyl-D-aspartate (NMDA) receptors, a subtype of glutamate receptors, on working memory. Rats were tested on the delayed nonmatching-to-position task in adulthood after repeated treatment of a noncompetitive NMDA antagonist MK-801 in postnatal days 7-20. As a result, this treatment led to deficits in learning and/or performance of delayed nonmatching-to-position responses, suggesting that chronic neonatal NMDA antagonism persistently impairs working memory. Furthermore, it decreased body and brain weight, and induced stereotyped head-rotation behavior. As working memory deficits are shown in several mental disorders such as schizophrenia and developmental disorders, rats with chronic neonatal NMDA antagonism might be useful for a better understanding of these disorders.