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.
Department of Pharmacology, School of Medical Sciences, Bristol, U.K.
W P
WP
Watson
H J
HJ
Little
D015761:4-Aminopyridine; D000628:Aminophylline; D000818:Animals; D000431:Ethanol / Q000009:adverse effects* / Q000378:metabolism; D007608:Kainic Acid; D008297:Male; D051379:Mice; D011963:Receptors, GABA-A / Q000187:drug effects; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D012640:Seizures / Q000209:etiology*; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology*
D011963:Receptors, GABA-A; D016194:Receptors, N-Methyl-D-Aspartate; D000628:Aminophylline; D000431:Ethanol; D015761:4-Aminopyridine; D007608:Kainic Acid