Interactions between RO 15-4513 and ethanol on brain self-stimulation and locomotor activity in rats

Experiments were conducted to elucidate the behavioral effects of RO 15-4513, a putative alcohol antagonist, when administered alone or in combination with alcohol. Two groups of animals were trained to lever-press for brain self-stimulation (ICSS) on either a fixed ratio:15 or a fixed interval:15 second schedule of reinforcement. RO 15-4513 (0.1-3.0 mg/kg) reduced the rate of lever-pressing for ICSS in both groups. RO 15-4513 (1.0 mg/kg) further reduced rates when combined with alcohol (0.1-1.7 g/kg), and this effect was especially marked in the fixed ratio paradigm. Other groups of animals were tested in a locomotor activity apparatus. In contrast to the depression of lever-pressing in the ICSS experiments, RO 15-4513 produced a graded increase in locomotor activity. When combined with alcohol (0.1-1.7 g/kg), 1.0 mg/kg RO 15-4513 also increased locomotor activity. Thus, the depression in schedule-controlled behavior was not associated with a generalized behavioral depression. These results demonstrated that RO 15-4513 has potent behavioral effects of its own that are consistent with its classification as an anxiogenic compound.