ly-303070 and Substance-Withdrawal-Syndrome

We have previously demonstrated that kainate receptors (KA-Rs) are acutely inhibited by ethanol (EtOH). Here we show that KA-Rs are also affected by long-term EtOH exposure. Whole-cell recordings of pharmacologically isolated KA-R-mediated currents in cultured hippocampal neurons revealed that exposure to 80 mM EtOH for 3 days followed by a 24 h withdrawal period increased KA-R current densities. Quantitative confocal microscopy showed that expression of GluR6/7 subunits increases after ethanol withdrawal in these neurons. Since KA-Rs control hippocampal excitability and seizure generation, we postulate that upregulation of these receptors may have a role in the pathophysiology of alcohol withdrawal syndrome.

Topics: Animals; Benzodiazepines; Cells, Cultured; Central Nervous System Depressants; Ethanol; Hippocampus; Membrane Potentials; Neurons; Patch-Clamp Techniques; Rats; Receptors, Kainic Acid; Substance Withdrawal Syndrome; Up-Regulation