The ability of chlordiazepoxide to maintain ethanol tolerance and dependence

Two criteria need to be satisfied in the demonstration of cross-dependence to chlordiazepoxide (CDP) in ethanol-dependent mice. These are the ability of CDP to suppress ethanol withdrawal and to maintain the dependent state. In this study, mice which had been fed chronically an ethanol diet followed by two days of CDP diet treatment had more severe CDP withdrawal signs induced by Ro15-1788 than drug-naive mice which were similarly exposed to the CDP diet treatment. The data indicate that CDP can maintain the dependent state acquired from the prior ethanol treatment. Alternatively, the prior ethanol treatment would have facilitated the development of CDP dependence, but it was not deemed likely. Three behavioral tests, namely, runway, sleep time, and drug-induced hypothermia, were used to test whether CDP could maintain the ethanol tolerance acquired from the prior ethanol treatment. The runway test showed that CDP could maintain the previously acquired ethanol tolerance. However, interpretations of the data from the sleep time and hypothermia tests are more equivocal because of factors such as peak tolerance, differential rates of development and dissipation of ethanol (or CDP) tolerance as determined by different behavioral tests.