Two models of ethanol withdrawal kindling.

The phenomenon of ethanol withdrawal kindling was examined using two different paradigms of ethanol treatment in rats and mice. In the first protocol, male Wistar rats were treated by ethanol inhalation for 14 days before withdrawal. Ethanol exposure was repeated three times with two days abstinence between treatments. In the second protocol, male C57BL/6 mice were fed liquid diet (Lieber DeCarli) containing 6.5%(v/v) ethanol for ten days. Feeding was repeated five times separated by 24 hr intervals. After both treatments, either spontaneous or handling-induced withdrawal behaviours were significantly intensified by sequential withdrawals. These results support the kindling hypothesis of ethanol withdrawal and provide models to develop potential pharmacological tools to attenuate enhanced withdrawal severity and to study the molecular mechanisms underlying this phenomenon.