Identification of distinct components, with different time courses, of the changes in response to convulsive stimuli during ethanol withdrawal.

The time courses of changes in sensitivity to handling-induced hyperexcitability, audiogenic seizures and a variety of chemical convulsants were compared in mice during a 24-hr period after withdrawal from chronic ethanol treatment. The peak increase in handling-induced hyperexcitability was seen between 3 and 5 hr after the withdrawal, disappearing by 12 hr, whereas the peak sensitivity to an audiogenic stimulus was found 8 hr into the withdrawal period. No changes were seen in thresholds to bicuculline during the 24-hr study. The thresholds to N-methyl-D-aspartate were decreased during the withdrawal period, with a maximum change at the 16-hr interval. In contrast, the thresholds to aminophylline were increased at 4 hr into withdrawal. The thresholds to 4-aminopyridine were also increased, with maximum changes at the 8-hr and 12-hr intervals. The only alterations in sensitivity to methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate and kainate were increases in the thresholds immediately on withdrawal, which were likely to have been due to residual ethanol. The results indicate that a complex pattern of neuronal changes occurs during ethanol withdrawal with a series of alterations in responses to convulsive stimuli which differ both in direction and in time course, suggesting different underlying mechanisms.