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 hyperex citability, audiogenic seizures and a variety of chemical convulsants were compared in mice during a 24-hr period after withdrawal from chro nic ethanol treatment. The peak increase in handling-induced hyperexci tability was seen between 3 and 5 hr after the withdrawal, disappearin g by 12 hr, whereas the peak sensitivity to an audiogenic stimulus was found 8 hr into the withdrawal period. No changes were seen in thresh olds to bicuculline during the 24-hr study. The thresholds to N-methyl -D-aspartate were decreased during the withdrawal period, with a maxim um change at the 16-hr interval. In contrast, the thresholds to aminop hylline were increased at 4 hr into withdrawal. The thresholds to 4-am inopyridine were also increased, with maximum changes at the 8-hr and 12-hr intervals. The only alterations in sensitivity to 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 o f neuronal changes occurs during ethanol withdrawal with a series of a lterations in responses to convulsive stimuli which differ both in dir ection and in time course, suggesting different underlying mechanisms.