Opposite Effects of Ro 15‐4513 on Acquisition and Maintenance of Ethanol Drinking Behavior in Male Wistar Rats

Abstract

Acute treatment with Ro 15-4513, a benzodiazepine receptor inverse agonist, has been consistently shown to suppress ethanol self administration behavior by rats. The aim of the present study was to examine the effect of Ro 15-4513 on the acquisition and maintenance of ethanol drinking behavior in male Wistar rats. In rats maintained on a limited access procedure with a choice of 12% w/v ethanol solution and water, acute treatment with Ro 15-4513 (0.1 to 3.0 mg/kg) suppressed ethanol intake in a selective and dose-related manner (p < 0.01). However, by the fourth day of chronic Ro 15-4513 treatment, ethanol intake had returned to baseline levels. In contrast, chronic administration of Ro 15-4513 during the acquisition phase increased ethanol drinking behavior, compared with vehicle (p < 0.05). To assess whether the effects of Ro 15-4513 on ethanol intake were due to an alteration in ethanol kinetics or on behavior, blood ethanol levels and rat social interaction behavior were also assessed. Neither acute nor chronic Ro 15-4513 treatment significantly altered ethanol kinetics after oral administration of ethanol (1.0 g/kg), but did suppress locomotor activity and time spent engaged in active social interaction at the 1.0 and 3.0 mg/kg doses. These results show that Ro 15-4513 has opposite effects on ethanol consumption during the acquisition and maintenance phases of ethanol drinking behavior, suggesting that different mechanisms regulate Ro 15-4513's effects on acquisition and maintenance of ethanol intake. Ro 15-4513's reported anxiogenic or memory enhancing properties may be responsible for its effects on acquisition.