Antagonism of ethanol-reinforced behavior by the benzodiazepine inverse agonists Ro15-4513 and FG 7142: relation to sucrose reinforcement.

The partial inverse benzodiazepine agonist Ro15-4513 has been shown to antagonize many of ethanol's actions, including the reduction of behavior reinforced with ethanol presentation. The studies reported here compared the effects of the Ro compound on sucrose reinforcement alone and concurrently available with ethanol reinforcement. Also, a second inverse agonist, FG 7142, was tested. The result indicated that ethanol reinforcement was more sensitive to the inverse agonists compared to sucrose reinforcement. This was seen as a graded effect upon ethanol responding at doses which failed to have any effect upon sucrose-reinforced behavior. The Ro compound was approximately three times more potent than the FG compound in suppressing ethanol-reinforced responding. Possible explanations for the greater sensitivity of ethanol reinforcement compared to sucrose reinforcement was discussed in terms of ethanol's potential actions at the benzodiazepine-GABA receptor complex.