Ethanol, at concentrations up to 88mM (~0.4% blood ethanol concentration), had no significant effect on evoked or spontaneous AMPA-mediated EPSCs (Fig. 4). Inhibitory currents mediated by the synaptic release of GABA were also largely insensitive to high concentrations of ethanol and no effects were observed in the paired pulse ratio of evoked GABA responses or in the frequency or amplitude of spontaneous GABAA IPSCs. These studies also showed no evidence for a tonic GABA-mediated current in deep-layer PFC pyramidal neurons or any effect of ethanol on the holding current that would have been expected if ethanol-sensitive extrasynaptic GABAA receptors were present. In contrast to these effects, ethanol inhibited stimulus-evoked NMDA-mediated EPSCs with significant effects occurring at concentrations of 22mM (~0.1% blood ethanol concentration) and above. Unlike that found in the slice cultures, there was no evidence for any rebound in activity following ethanol washout for any of the synaptic currents examined. These results suggest that NMDA receptors are a particularly important target for the acute effects of ethanol on PFC pyramidal neuron function and that ethanol’s inhibition of persistent activity in slice cultures is a result of this effect. This is consistent with the ability of a low concentration of
