Ro 15-4513, like anxiogenic beta-carbolines, increases dopamine metabolism in the prefrontal cortex of the rat

The effects of Ro 15-4513, FG 7142 and beta-CCM on the activity of the mesocortical dopaminergic system were examined by measuring the changes in the content of the principal dopamine (DA) metabolite, dihydroxyphenylacetic acid (DOPAC) in the prefrontal cortex of the rat. Ro 15-4513 increased the DOPAC content in the prefrontal cortex in a dose-dependent manner (5-40 mg/kg i.p.) but had no effect on DA concentrations. A similar increase in DOPAC content was induced by FG 7142 (40 mg/kg i.p.) and beta-CCM (8 mg/kg s.c.), two beta-carboline derivatives that interact with benzodiazepine recognition sites as partial inverse agonists. These effects of Ro 15-4513, FG 7142 and beta-CCM on DA metabolism in the prefrontal cortex are mediated via benzodiazepine recognition sites, since they were prevented by the administration of the benzodiazepine antagonists Ro 15-1788 and ZK 93426. These data indicate that Ro 15-4513 is an inverse agonist at benzodiazepine recognition sites.