Diazepam prevents progression of kindled alcohol withdrawal behaviour

The purpose of the present experiment was to study the "kindling" hypothesis of alcohol withdrawal stating that exposure to repeated episodes of alcohol withdrawal results in an increased severity of subsequent withdrawal reactions. Two groups of male Wistar rats were subjected to 13 episodes of 2 days severe alcohol intoxication and 5 days alcohol withdrawal. Animals in the control group (n = 80) developed clinical withdrawal signs following each intoxication episode. In the diazepam group (n = 80) the withdrawal reactions during episodes 1-9 were blocked by intraperitoneal diazepam administration (0-30 mg/kg) 8, 11 and 15 h into withdrawal. During episode 10-13 diazepam treatment was terminated and convulsive withdrawal behaviour was observed 9-15 h after last alcohol dose. The probability of seizure activity during these four withdrawal episodes was calculated as 0.239 and 0.066 in the control and the diazepam groups, respectively. Based on Monte Carlo simulation techniques, this difference was found to be statistically significant (P < 0.05). No differences in the non-convulsive alcohol withdrawal symptoms tremor, hyperactivity and rigidity were detected between controls and diazepam animals after diazepam treatment. It was concluded that the increased convulsive behaviour in the control group was caused by cumulated kindling-like cerebral alterations during the previous repeated alcohol withdrawal phases.