Chronic exposure of cerebellar granule cells to ethanol results in increased N-methyl-D-aspartate receptor function
Iorio, K.R.; Reinlib, L.; Tabakoff, B.; Hoffman, P.L.
Molecular Pharmacology 41(6): 1142-1148
ISSN/ISBN: 0026-895X PMID: 1535416 Accession: 008316059
In primary cultures of cerebellar granule cells, activation of the N-methyl-D-aspartate (NMDA) receptor leads to Ca-2+ influx. Previous work showed that this response is selectively inhibited by acute exposure to low concentrations of ethanol. The present results demonstrate that the response to NMDA (measured as an increase in intracellular Ca-2+ concentration, using fura-2 fluorescence) is significantly enhanced after chronic in vitro exposure of the cells to ethanol (100 mm for 2-4 days; 20 mm for 3 or more days). This enhancement is consistent with an increased number of NMDA receptors, with no change in receptor properties. Specifically, there was no change in the EC-50 values for NMDA and glycine or in the magnitude of inhibition of the NMDA response by competitive or uncompetitive antagonists. There was also no change in the ability of acute ethanol to inhibit the NMDA response after chronic exposure of the cells to ethanol. Furthermore, chronic ethanol exposure did not alter depolarization-dependent increases in intracellular Ca-2+ observed after exposure of the cells to 30 mm KCl. The data suggest that chronic ethanol exposure produces a selective up-regulation of NMDA receptor function. In the intact animal, such a change may be associated with particular symptoms of ethanol withdrawal, i.e., withdrawal seizures.