Repeated
ethanol withdrawal experience has been shown to result in an exacerbation of future withdrawal episodes. This sensitization of the withdrawal response has been hypothesized to represent a "kindling" phenomenon. The present study was designed to examine whether a systematic increase in the number of previous
ethanol withdrawal experiences increases both the severity and duration of a subsequent withdrawal response. An established model of repeated
ethanol intoxication/withdrawal was employed in which adult C3H mice were chronically exposed to
ethanol vapor in inhalation chambers. In the first experiment, multiple withdrawal (MW) groups of mice received nine (MW x 9), six (MW x 6), or three (MW x 3) cycles of 16-h
ethanol vapor separated by 8-h periods of abstinence prior to testing: a single withdrawal (SW) group was tested following a single bout of 16-h
ethanol exposure; and a control (C) group did not receive any
ethanol treatment throughout the experiment. In a second experiment, a group of mice (MW1-9) were repeatedly tested over nine cycles of withdrawal. A third experiment was designed to assess the effects of repeated
pyrazole administration on the potentiated withdrawal seizure response. Results indicated a positive relationship between the number of previously experienced
ethanol withdrawals and the severity and duration of a subsequent withdrawal episode. Blood
ethanol levels were similar for all
ethanol-exposed groups prior to withdrawal assessment. Further, the intensity of withdrawal
seizures (handling-induced convulsions) progressively increased over nine cycles of intoxication/withdrawal and repeated testing did not significantly influence the development of this potentiated response. In addition, repeated administration of
pyrazole did not appear to influence this withdrawal sensitization phenomenon. Collectively, these results provide further support for the "kindling" hypothesis of
ethanol withdrawal.