Time Course of Acamprosate Action on Operant Ethanol Self-Administration after Ethanol Deprivation

The effects of the new alcohol anticraving compound acamprosate on the alcohol deprivation effect were tested in an operant two-lever free choice paradigm with concurrent water. Two groups of rats were tested after long-term voluntary ethanol self-administration: the "continuous access" group consisting of animals that had continuous access to ethanol before operant testing; and the "limited access" group that was tested only after ethanol deprivation. The limited access group exhibited a strong alcohol deprivation effect with immediate high ethanol consumption and preference. Acamprosate (100, 200, or 400 mg/kg) dose-dependently reduced lever pressing for ethanol and, accordingly, ethanol consumption in both groups in a 23-hr session. The consumption-reducing effect was still evident at the end of the session. Ethanol preference was dose-dependently reduced during the first hour of the session, but returned to basal levels before the end of the 23-hr session in both groups. Thus, the time course of preference reduction was not identical with that of the reduction of ethanol consumption. Surprisingly, preference reduction was observed only after a considerable amount of ethanol had been consumed. These results suggest that the specific effect of preference reduction depended on the simultaneous presence of sufficient levels of acamprosate and ethanol, and that the longer-lasting reduction of ethanol consumption was the consequence of this experience.