IRREVERSIBILITY OF KINDLED ALCOHOL-WITHDRAWAL BEHAVIOUR IN RATS

In order to investigate whether alcohol-withdrawal kindling is an irreversible process, male Wistar rats were exposed to 12 episodes, each consisting of 2 days of severe alcohol intoxication and 5 days of alcohol withdrawal. Spontaneous withdrawal seizures were found in 15% of the animals during episodes 10–12. After an alcohol-free period of 26 days, the animals were subjected to three more episodes of alcohol dependence (i.e. episodes 13–15) in which 12% of the animals developed spontaneous withdrawal seizures. Based on several statistical tests, we concluded that there was no true difference between the seizure activity in episodes 10–12 and episodes 13–15, indicating that alcohol-withdrawal kindling is a long-lasting and perhaps irreversible process. In a second experiment, an alcohol-withdrawal kindled group was first exposed to seven episodes of alcohol dependence. A diazepam group went through the same alcohol regimen, but each withdrawal reaction was blocked by diazepam treatment. Finally, a single episode group was included which 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 differences across the groups. These results call for a modification of the kindling hypothesis of alcohol withdrawal and suggest that kindling-induced alterations may be overlooked if convulsive behaviour is tested during a relatively strong withdrawal reaction.