REPEATED ETHANOL WITHDRAWAL EXPERIENCE INCREASES THE SEVERITY AND DURATION OF SUBSEQUENT WITHDRAWAL SEIZURES IN MICE

Repeated ethanol withdrawal experience has been shown to result in an exacerbation of future withdrawal episodes. This sensation of the with drawal response has been hypothesized to represent a ''kindling'' phen omenon. The present study was designed to examine whether a systematic increase in the number of previous ethanol withdrawal experiences inc reases both the severity and duration of a subsequent withdrawal respo nse. An established model of repeated ethanol intoxication/withdrawal was employed in which adult C3H mice were chronically exposed to ethan ol vapor in inhalation chambers. In the first experiment, multiple wit hdrawal (MW) groups of mice received nine (MWx9), six (MWx6), or three (MWx3) cycles of 16-h ethanol exposure; and a control (C) group did n ot receive any ethanol treatment throughout the experiment. In a secon d experiment, a group of mice (MW1-9) were repeatedly tested over nine cycles of withdrawal. A third experiment was designed to assess the e ffects of repeated pyrazole administration on the potentiated withdraw al seizure response. Results indicated a positive relationship between the number of previously experienced ethanol withdrawals and the seve rity and duration of a subsequent withdrawal episode. Blood ethanol le vels were similar for all ethanol-exposed groups prior to withdrawal a ssessment. Further, the intensity of withdrawal seizures (handling-ind uced convulsions) progressively increased over nine cycles of intoxica tion/withdrawal and repeated testing did not significantly influence t he development of this potentiated response. In addition, repeated adm inistration of pyrazole did not appear to influence this withdrawal se nsitization phenomenon. Collectivity, these results provide further su pport for the ''kindling'' hypothesis of ethanol withdrawal.