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Abstract
The time course of ethanol-induced inhibition of NMDA-mediated synaptic activity was
studied in brain slices using extracellular electrophysiological techniques in the
CA1 region of the hippocampus. Bath application of 60 mM ethanol inhibited NMDA-mediated
field excitatory postsynaptic potentials (EPSPs) by at least 45% in 7/11 of the slices
tested, with the remaining 4 slices inhibited by 8.7-35%. Most slices inhibited by
at least 45% showed a significant reduction in ethanol inhibition over a 15 min ethanol
exposure period, suggesting the development of acute tolerance. In a second set of
experiments, tolerance to ethanol-induced inhibition of NMDA-mediated EPSPs that developed
over time during the first ethanol exposure persisted during a second ethanol exposure.
In contrast to ethanol, inhibition of EPSPs by the NMDA antagonist DL-2-amino-5-phosphonopentanoic
acid (APV) remained stable during a comparable application of the drug. These results
suggest that acute tolerance can develop to ethanol inhibition of NMDA mediated synaptic
activity in the hippocampus.