Printed in the U . S . A . DISCRIMINATIVE AND AVERSIVE PROPERTIES OF 8 - CARBOLINE - 3 - CARBOXYLIC ACID ETHYL ESTER , A BENZODIAZEPINE RECEPTOR INVERSE AGONIST , IN RHESUS MONKEYS

Rhesus monkeys were trained to discriminate injections of saline from those of 8-carboline-3-carboxylic acid ethyl ester (8-CCE), a compound that binds to the benzodiazepine receptor, but often has actions opposite to those of the benzodiazeplnes. A benzodlazepine agonist midazolam and low doses of a specific benzodiazepine antagonist, Ro 15-1788, reversed the discriminative effects of 8-CCE. Higher doses of Ro 15-1788 produced stimulus effects similar to ~-CCE. In a separate experiment, monkeys responded to terminate intravenous infusions of 8-CCE, but not mldazolam. This averslve effect of 8-CCE was~ reversed by RO 15-1788. The behavioral effects of 8-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 8-CCE can be considered an inverse agonist at this receptor.