Alcohol withdrawal seizures: implications of kindling.

The periodic administration of convulsive agents, even at doses or intensities that initially have no convulsive effect, can lead to a progressive and enduring increase in the susceptibility to subsequent convulsive stimulation. This kindling effect has contributed to the understanding of the convulsive effects of alcohol withdrawal in three ways. First, rats kindled by the periodic application of electroconvulsive shock, local brain stimulation, or pentylenetetrazol were found to be hypersusceptible to the convulsive effects of subsequent alcohol withdrawal, thus raising the possibility that some forms of electrical or pharmacological therapy can potentiate the alcohol withdrawal syndrome in humans. Second, the duration of seizures elicited in kindled rats has been used as a sensitive index of convulsive withdrawal effects; increases in the duration of kindled motor seizures and afterdischarges can be detected following the metabolism of a single intoxicating injection of ethanol. Third, it was suggested that the potentiation of the convulsive effects of alcohol exposure and withdrawal by prior episodes of alcohol withdrawal may reflect a kindling-like process rather than an increase in physical dependence.