The effect of repeated withdrawal episodes on subsequent withdrawal severity in ethanol-treated rats.

Male rats were given ethanol via an intragastric catheter (8.0-11.0 g/kg per day) for either 8 weeks daily or for four 2-week periods with a 2-week period of no drug treatment intervening between each period of ethanol administration (binge). Older rats were administered ethanol for 2 weeks, to assess the effects of age on ethanol withdrawal as age can alter an animal's sensitivity to ethanol. The presence of physical dependence during withdrawal was assessed on an open field test. Rats that experienced repeated episodes of withdrawal (binge) showed more severe withdrawal signs in successive withdrawal episodes. Older animals showed more severe signs of withdrawal than younger animals after 2 weeks of ethanol treatment. The results of this study lend support to the hypothesis that the experience of withdrawal from ethanol can alter an animal's subsequent response to the drug. Aging appeared to contribute to this effect, but further work is needed to delineate its role.