Partial cross-dependence on ethanol in mice dependent on chlordiazepoxide.

Mice which had been fed chronically a liquid diet containing chlordiazepoxide (CDP) showed spontaneous and Ro15-1788-induced withdrawal signs upon CDP withdrawal. Ethanol (1.5 g/kg) injected 5 min before Ro15-1788 injection almost completely suppressed the withdrawal signs induced by the benzodiazepine receptor antagonist. However, neither ethanol injection nor ethanol diet administration could prevent the loss of appetite and weight loss on day 1 of CDP withdrawal. Likewise, the addition of saccharin in the ethanol diets did not prevent the loss of appetite. Mice which had been fed the CDP diet followed by 9 days of ethanol treatment (CDP/ethanol) showed more severe hypothermia during ethanol withdrawal compared to mice which had been fed the control/ethanol diets. The CDP/ethanol mice also retained the increase in runway activity attained from the prior CDP treatment. The data indicate that CDP-dependent mice showed partial rather than full cross-dependence on ethanol.