POSTNATAL PHENCYCLIDINE TREATMENT DIFFERENTIALLY REGULATES N-METHYL-D-ASPARTATE RECEPTOR SUBUNIT MESSENGER-RNA EXPRESSION IN DEVELOPING RATCEREBRAL-CORTEX

The present study was designed to determine the effects of chronic neo natal exposure to the NMDA receptor antagonist phencyclidine (PCP) on [H-3]MK-801 binding and on gene expression of NMDA receptor subunits i n juvenile male rats. Rat pups were injected daily with PCP from day 5 to 15 and killed on day 21. [H-3]MK-801 binding was measured by quant itative autoradiography. A sensitive RNase protection assay was employ ed to determine simultaneously the mRNA levels of NR1 subunit (compris ing all different splice variants) and three NR2 subunits (NR2A-NR2C). The relative distribution profile of NMDA receptor subunits in the ce rebral cortex was NR2B > NR1 > NR2A > NR2C and in the cerebellum NR2C = NR1 > NR2A = NR2B. Chronic PCP administration in postnatal rats prod uced significant reduction in both [H-3]MK-801 binding and mRNA level of the NR2B subunit in the cerebral cortex. Expression of the other NM DA receptor subunits in the cerebral cortex did not change following t he drug treatment. In the cerebellum, neither [H-3]MK-801 binding nor any of the NMDA receptor subunit expression levels showed any alterati on. Together, these data provide a molecular correlate for chronic pos tnatal PCP-induced down-regulation of [H-3]MK-801 binding in rat cereb ral cortex and suggest that the NR2B subunit plays an important role i n developmental plasticity.