CHRONIC ETHANOL TREATMENT DIFFERENTIALLY REGULATES NMDA RECEPTOR SUBUNIT MESSENGER-RNA EXPRESSION IN RAT-BRAIN

Previous studies have implicated the N-methyl-D-aspartate receptor (NM DAR) complex in the physical dependence and withdrawal effects of chro nic ethanol administration. In this study, we examined the effect of c hronic ethanol administration and ethanol withdrawal on the NMDAR subu nit R1, R2A, R2B, and R2C mRNA levels in rat hippocampus, cerebral cor tex, and cerebellum. Using the RNase protection assay, we compared the levels of the NMDAR subunits mRNAs in ethanol-treated and control rat s. Our results indicate that chronic ethanol administration and ethano l withdrawal do not change the NMDAR R1 subunit mRNA levels in cerebra l cortex, hippocampus, or cerebellum at any time point. In contrast, 9 h after the last ethanol administration the R2A and R2B mRNA subunits were elevated by approximate to 40% in cerebral cortex, and approxima te to 30% in hippocampus with respect to the levels in control animals . At 48 h the mRNA levels returned to the control levels. The chronic ethanol treatment did not alter R1, R2A, and R2C subunit mRNA levels i n cerebellum. Our results demonstrate that chronic ethanol administrat ion produces a differential regulation of the genes encoding the vario us subunits of the NMDAR.