CHRONIC ETHANOL-MEDIATED UP-REGULATION OF THE N-METHYL-D-ASPARTATE RECEPTOR POLYPEPTIDE SUBUNITS IN MOUSE CORTICAL-NEURONS IN CULTURE

The goal of this study was to determine whether chronic ethanol-mediat ed up-regulation of the N-methyl-D-aspartate receptors (NMDAR) was ass ociated with an augmentation of the NMDAR polypeptide subunits in the mammalian cortical neurons. The results show that chronic ethanol trea tment produced an increase in the R1 and R2B polypeptide subunits. The R2A subunit was not expressed in these neurons. Chronic NMDAR antagon ist (+)-3-2-(carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP)) tre atment also increased the R1 and R2B polypeptide subunits. A similar i ncrease was observed when ethanol and CPP were used in combination. Bi nding studies using [H-3]MK-801 ((+)-5-methyl-10,11-dihydro -5H-dibenz o[a,d]cyclophenptan-5,10-imine maleate), a noncompetitive NMDAR antago nist, confirmed that concomitant exposure of ethanol and CPP up-regula ted the NMDAR. Our results demonstrate for the first time that chronic ethanol treatment increased the NMDA receptor polypeptide subunit syn thesis and that it was associated with an increase in [H-3]MK-801 bind ing sites.