title: Increased NMDA receptor and calcium channel activity underlying ethanol withdrawal hyperexcitability.
abstract: 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.
authors.affiliation: Department of Pharmacology, Medical School, University Walk, Bristol, UK.
authors.forename: M A
authors.initials: MA
authors.lastname: Whittington
authors.forename: J D
authors.initials: JD
authors.lastname: Lambert
authors.forename: H J
authors.initials: HJ
authors.lastname: Little
mesh_terms: D000818:Animals; D001143:Arousal; D015220:Calcium Channels / Q000187:drug effects*; D000431:Ethanol / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects; D008297:Male; D051379:Mice; D017966:Pyramidal Cells / Q000187:drug effects; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects*; D013375:Substance Withdrawal Syndrome; D009435:Synaptic Transmission / Q000187:drug effects; D013997:Time Factors
chemical_list: D015220:Calcium Channels; D016194:Receptors, N-Methyl-D-Aspartate; D000431:Ethanol