Discriminative and aversive properties of β-carboline-3-carboxylic acid ethyl ester, a benzodiazepine receptor inverse agonist, in rhesus monkey

Rhesus monkeys were trained to discriminate injections of saline from those of β-carboline-3-carboxylic acid ethyl ester (β-CCE), a compound that binds to the benzodiazepine receptor, but often has actions opposite to those of the benzodiazepines. A benzodiazepine agonist midazolam and low doses of a specific benzodiazepine antagonist, Ro 15-1788, reversed the discriminative effects of β-CCE. Higher doses of Ro 15-1788 produced stimulus effects similar to β-CCE. In a separate experiment, monkeys responded to terminate intravenous infusions of β-CCE, but not midazolam. This aversive effect of β-CCE was reversed by Ro 15-1788. The behavioral effects of β-CCE in these non-human primates are consistent with other data that have shown it to act on benzodiazepine receptors, and support the hypothesis that β-CCE can be considered an inverse agonist at this receptor.