Substitution of chlordiazepoxide for ethanol in alcohol-dependent mice

Alcohol dependence was induced in C57BL/6J mice by administration of a liquid diet containing ethanol. These mice showed alcohol withdrawal signs when the alcohol diet was withdrawn. However, when the alcohol diet was substituted with three liquid diets containing different amounts of chlordiazepoxide (CDP; 0.4, 1 and 2 mg/ml), the alcohol withdrawal signs were fully suppressed by CDP. The CDP diet administration was continued for 14-24 days. At termination of the diet treatment, the mice showed CDP withdrawal signs. Similar signs, but much more short-lived, can be precipitated by injection of the benzodiazepine receptor antagonist, RO-15-1788. The results are consistent with the hypothesis that alcohol-dependent mice are cross-dependent on CDP. This report constitutes the first experimental demonstration of cross-dependence between ethanol and CDP. The reverse phenomenon, namely, CDP-dependent mice being cross-dependent on ethanol, remains to be investigated.