Acute tolerance to ethanol inhibition of NMDA-mediated EPSPs in the CA1 region of the rat hippocampus.

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.