Convulsive behaviour during alcohol dependence: discrimination between the role of intoxication and withdrawal

Male Wistar rats were subjected to repeated weekly episodes of 2 days severe alcohol intoxication (intragastric intubation) and 5 days of withdrawal. In half of the animals the withdrawal reaction was attenuated during the first nine weekly episodes by intragastric intubations with phenobarbital. During episodes 10-14 both phenobarbital treated and phenobarbital untreated animals were allowed to develop a withdrawal reaction; all animals were video-recorded during withdrawal and the records were rated blindly for the occurrence of convulsive seizures. The results were analyzed by step-wise logistic analysis of regression including phenobarbital treatment, alcohol dose and intoxication score as explanatory variables for the occurrence of convulsive seizures. The animals that had been in withdrawal during all episodes developed significantly more convulsive seizures compared with animals that had their first nine withdrawal episodes attenuated by phenobarbital. The development of withdrawal seizures depended on repeated episodes of withdrawal, whereas repeated alcohol intoxication per se did not explain the development of seizures. There were no differences between the groups in the severity of the non-convulsive signs of alcohol withdrawal. Thus the development of seizures and the non-convulsive signs of alcohol withdrawal may result from two pathogenetically different mechanisms: 1) seizures from a cumulative kindling-like effect over long time periods and 2) physical signs of alcohol withdrawal may reflect the degree of physical dependence during the most recent drinking bout.