Proconvulsant and anticonvulsant properties of ethanol: studies of electrographic seizures in vitro

Recent studies have demonstrated that ethanol is a potent blocker of N-methyl-D-aspartate (NMDA) receptor mediated responses. It is well known that neuroplasticity processes depend on the activation of the NMDA type of excitatory amino acid receptor. We have used an in vitro model of electrographic seizures (EGS), a neuroplasticity process, to examine the effect of varying ethanol concentrations. In the present experiment, slices of rat hippocampus were electrically stimulated to produce stimulus train-induced epileptiform bursting in area CA3. EGS duration and intensity was enhanced by 10 mM ethanol, whereas increasing the concentration of ethanol (60-300 mM) attenuated established EGSs. Ethanol also raised the threshold to elicit an EGS. Removal of low ethanol concentrations resulted in a hyperexcitable state, with increased EGS duration and intensity. These results reflect acute biphasic effects of ethanol across concentrations, and withdrawal hyperexcitability. The effects of ethanol on EGSs, at concentrations which elicit intoxication but not anesthesia (< 75 mM), resemble the actions produced by NMDA antagonists on EGSs. Therefore the effects of ethanol on stimulus train-induced EGSs may be mediated through an action at the NMDA receptor complex.