Effects of Ro 15-4513 and ethanol on operant behavior of male and female C57BL/6 mice

Abstract

Although the partial benzodiazepine receptor inverse agonist, Ro 15-4513, counteracts many ethanol effects, its effect on operant behavior or on ethanol-induced changes in this behavior, remains controversial. In this study, we examined the effects of Ro 15-4513, ethanol, and their interaction on behavior maintained by an FR 20 schedule of food reinforcement. Ro 15-4513 (1.0-4.0 mg/kg) and ethanol (1.5-3.0 g/kg) reduced lever-responding of both male and female mice. The disruptive effect of Ro 15-4513 was of short duration (approximately 10 min), and was greater in male than in female mice. Under equivalent dose and time parameters, ethanol disrupted behavior of both sexes to the same extent. In spite of the disruptive effects of both drugs when given alone, when given after ethanol and prior to testing, Ro 15-4513 attenuated the disruptive effects of ethanol in male mice. The present study extends previous reports by documenting: (1) that the disruptive effect of Ro 15-4513 on mice is of very short duration and occurs at lower doses than previously reported; (2) that, in spite of being disruptive itself, Ro 15-4513 can attenuate the disruptive effects of ethanol on schedule controlled behavior; and (3) that gender is an important consideration in determining the effects of this compound.