Postnatal phencyclidine treatment differentially regulates N-methyl-D-aspartate receptor subunit mRNA expression in developing rat cerebral cortex.
R Sircar, P Follesa, M K Ticku
Brain research. Molecular brain research September 1, 1996 DOI: 10.1016/0169-328x(96)00051-4 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental animal study Peer reviewed |
|---|---|
| Population | Juvenile male rats (pups injected from postnatal day 5 to 15, killed on day 21) |
| Intervention | Phencyclidine (PCP) |
| Duration | Daily injections from postnatal day 5 to 15; rats killed on day 21 |
| Measures | [3H]MK-801 binding (quantitative autoradiography), RNase protection assay for NR1, NR2A, NR2B, NR2C mRNA |
| Key findings | Chronic neonatal PCP administration reduced [3H]MK-801 binding and NR2B subunit mRNA in the rat cerebral cortex, while other cortical NMDA receptor subunits and all cerebellar measures were unchanged. The authors suggest NR2B plays an important role in developmental plasticity. |
Abstract
The present study was designed to determine the effects of chronic neonatal exposure to the NMDA receptor antagonist phencyclidine (PCP) on [3H]MK-801 binding and on gene expression of NMDA receptor subunits in juvenile male rats. Rat pups were injected daily with PCP from day 5 to 15 and killed on day 21. [3H]MK-801 binding was measured by quantitative autoradiography. A sensitive RNase protection assay was employed to determine simultaneously the mRNA levels of NR1 subunit (comprising all different splice variants) and three NR2 subunits (NR2A-NR2C). The relative distribution profile of NMDA receptor subunits in the cerebral cortex was NR2B > NR1 > NR2A > NR2C and in the cerebellum NR2C = NR1 > NR2A = NR2B. Chronic PCP administration in postnatal rats produced significant reduction in both [3H]MK-801 binding and mRNA level of the NR2B subunit in the cerebral cortex. Expression of the other NMDA receptor subunits in the cerebral cortex did not change following the drug treatment. In the cerebellum, neither [3H]MK-801 binding nor any of the NMDA receptor subunit expression levels showed any alteration. Together, these data provide a molecular correlate for chronic postnatal PCP-induced down-regulation of [3H]MK-801 binding in rat cerebral cortex and suggest that the NR2B subunit plays an important role in developmental plasticity.