ETHANOL AND REGULATION OF THE NMDA RECEPTOR SUBUNITS IN FETAL CORTICAL-NEURONS

Previous studies have shown that chronic ethanol treatment up-regulate s the expression of the N-methyl-D-aspartate (NMDA) receptor number an d function both in vitro and in vivo. In vitro chronic ethanol treatme nt specifically augments mRNA levels of the R2B subunit without alteri ng R1 subunit mRNA levels, although similar treatment results in incre ased levels of both R1 and R2B polypeptides. To further delineate the molecular mechanisms involved in differential regulation of NMDA recep tor subunits by chronic ethanol treatment (50 mM, 5 days), we have det ermined the mRNA stability of the NMDA R1 and R2B subunits and the tra nscription rate of the respective genes using mouse fetal cortical neu rons. Our observations demonstrated that ethanol stabilized the NMDA R 1 mRNA over the time period examined (24 h) without altering the stabi lity of the R2B mRNA. Chronic exposure of fetal cortical neurons to et hanol enhanced the rate of R2B gene transcription approximately twofol d. Taken together, these results suggest that up-regulation of the NMD A receptor number seen in cultured cortical neurons after chronic etha nol treatment is due to the regulation of the NMDA R2B receptor subuni t al the transcriptional level and that of the NMDA R1 subunit mainly at the posttranscriptional level.