REGIONAL AND SUBUNIT-SPECIFIC CHANGES IN NMDA RECEPTOR MESSENGER-RNA AND IMMUNOREACTIVITY IN MOUSE-BRAIN FOLLOWING CHRONIC ETHANOL INGESTION

Chronic ethanol treatment of mice has been shown to result in increase d binding of dizocilpine and glutamate to hippocampal NMDA receptors. These changes were suggested to reflect an increase in NMDA receptor n umber that may underlie certain signs of the ethanol withdrawal syndro me. However, there was no change in binding of a competitive NMDA rece ptor antagonist, or of ligand binding to the glycine co-agonist site o n the receptor after chronic ethanol treatment. Differential changes i n the binding of particular ligands at the NMDA receptor suggested the possibility that chronic ethanol ingestion might selectively affect t he expression of particular NMDA receptor subunits. Our current work d emonstrates that chronic ethanol ingestion by mice, which results in t he generation of physical dependence, also produces increases in the N MDA receptor NR1 subunit protein in the hippocampus and cerebellum (si milar to 50% and 95%, respectively), and produces increases in the NR2 A subunit protein in the hippocampus and cortex (similar to 25% and 40 %, respectively). However, the mRNA levels for these subunits were not increased in the respective brain areas by the same ethanol treatment . The changes in NMDA receptor subunit expression in discrete areas of the brain may contribute to the previously observed changes in ligand binding and, possibly, signs of ethanol withdrawal.