Effects of repeated MK-801 administration on the glutamate receptor gene expression in the rat hippocampus.

ABSTRACT

Effects of acute and chronic treatment with the noncompetitive NMDA receptor antagonist MK-801 on the NMDAR1 and GluR2 (flip and flop) receptor mRNA levels were estimated in the rat hippocampal formation. An in situ hybridization study showed that a single injection of MK-801 increased the NMDAR1 mRNA level in the CA1 region after 3 and 24 h, and in the CA3 one after 3 h, whereas chronic administration of the drug increased the mRNA level in the dentate gyrus and CA1 at the latter time. The level of the flip version of GluR2 mRNA was decreased in the CA3 region, and dentate gyrus at 3 and 24 h following acute MK-801 administration. Chronic MK-801 administration decreased GluR2 flip mRNA level in the dentate gyrus at 3 and 24 h, and in the CA1 region at 3 h only. On the other hand, chronic, but not acute, MK-801 administration elevated the GluR2 flop mRNA level in the CA1 region and dentate gyrus 24 h after the last drug injection. In summary, the above data indicate that both acute and chronic MK-801 administration affect the NMDAR1 and GluR2 receptor gene expression in the rat hippocampal formation in a time- and region-specific manner. These changes may, in turn, influence the glutamatergic transmission and/or susceptibility to the EAA-mediated excitotoxicity of hippocampal neurons.