interneurons. Using a slice co-culture system, it was shown that 44 mM ethanol significantly reduced the average duration of up-states in both types of neuron and had a variable effect on spiking, with a trend towards an increase in pyramidal neurons and a reduction in fast-spiking neurons [46]. Whole-cell recordings in rat cortical slices have been used to determine how ethanol modulates the GABAergic and glutamatergic components underlying persistent activity. Significant inhibition of NMDA receptor-mediated evoked excitatory postsynaptic currents (eEPSCs) was seen after administration of 22 mM ethanol, while concentrations of ethanol up to 44 mM had no effect on AMPA receptor-mediated evoked EPSCs or GABA receptor-mediated IPSCs [47]. This indicates that ethanol primarily affects the postsynaptic NMDA receptor-mediated component of the glutamatergic response. Finally, a contribution of glycine receptors to the inhibitory actions of acute alcohol has been observed. In layer V pyramidal neurons in the mouse lateral orbital frontal cortex, acute alcohol (33–66 mM) reduces neuronal excitability, surprisingly not through an NMDA or GABAergic mechanism, but by acting on a population of strychnine-sensitive glycine receptors that carry a tonic inhibitory current [40, 48] that is known to be present in the frontal cortex [49].
