Increased NMDA receptor and calcium channel activity underlying ethanol withdrawal hyperexcitability

Withdrawal from chronic ethanol administration results in hyperexcitability. In the hippocampus, evoked bursting activity and spontaneous epileptiform events are seen. The present study investigated the effect of ethanol withdrawal on N-methyl-D-aspartate (NMDA) receptor-mediated postsynaptic potentials and on voltage-gated calcium currents, in mouse hippocampal pyramidal cells. The NMDA receptor-mediated component of synaptic excitation was increased during withdrawal, accompanied by an increase in synaptic activation of calcium spikes. Evidence for a direct effect of ethanol withdrawal on calcium channel function was seen in voltage clamp recordings of isolated, slowly inactivating calcium currents. A synergistic effect of increased NMDA receptor and calcium channel function is therefore suggested to contribute to hyperexcitability during ethanol withdrawal.