FLUMAZENIL (RO15-1788) DOES NOT AFFECT ETHANOL TOLERANCE AND DEPENDENCE

There are conflicting reports concerning whether flumazenil (Ro15-1788) can antagonize the central effects of ethanol and ethanol withdrawal reactions. C57BL/6J mice were treated chronically with an ethanol liquid diet. Control mice were pair fed an isocaloric diet containing no ethanol. These mice were injected with either Ro15-1788 (25 mg/kg) or vehicle immediately before, 14 h or 24 h before ethanol withdrawal. Under these conditions, no attenuation of the severity of handling-induced withdrawal seizures or of withdrawal hypothermia was observed in the ethanol-dependent mice injected with Ro15-1788. Likewise, there was no abolition or attenuation of tolerance to the ataxic effects (sleep time and horizontal dowel tests) and hypothermic effects of ethanol by Ro15-1788 when the mice were tested on day 3 of ethanol withdrawal. It is concluded that Ro15-1788 (25 mg/kg) has no effect on ethanol tolerance and dependence.