IRREVERSIBILITY OF KINDLED ALCOHOL-WITHDRAWAL BEHAVIOR IN RATS

In order to investigate whether alcohol-withdrawal kindling is an irre versible process, male Wistar rats were exposed to 12 episodes, each c onsisting of 2 days of severe alcohol intoxication and 5 days of alcoh ol withdrawal. Spontaneous withdrawal seizures were found in 15% of th e animals during episodes 10-12. After an alcohol-free period of 26 da ys, the animals were subjected to three more episodes of alcohol depen dence (i.e. episodes 13-15) in which 12% of the animals developed spon taneous withdrawal seizures. Based on several statistical tests, we co ncluded that there was no true difference between the seizure activity in episodes 10-12 and episodes 13-15, indicating that alcohol-withdra wal kindling is a long-lasting and perhaps irreversible process. In a second experiment, an alcohol-withdrawal kindled group was first expos ed to seven episodes of alcohol dependence. A diazepam group went thro ugh the same alcohol regimen, but each withdrawal reaction was blocked by diazepam treatment. Finally. a single episode group was included w hich was fed isocalorically with the kindled animals. After an alcohol -free period of 11 days, all three groups were subjected to 4 days of severe alcohol intoxication. During the subsequent withdrawal reaction seizures were observed in 22-26% of the animals with no significant d ifferences across the groups. These results call for a modification of the kindling hypothesis of alcohol withdrawal and suggest that kindli ng-induced alterations may be overlooked if convulsive behaviour is re sted during a relatively strong withdrawal reaction.