Discriminative and aversive properties of beta-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 beta-carboline-3-carboxylic acid ethyl ester (beta-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 beta-CCE. Higher doses of Ro 15-1788 produced stimulus effects similar to beta-CCE. In a separate experiment, monkeys responded to terminate intravenous infusions of beta-CCE, but not midazolam. This aversive effect of beta-CCE was reversed by Ro 15-1788. The behavioral effects of beta-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 beta-CCE can be considered an inverse agonist at this receptor.
D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects*; D001569:Benzodiazepines / Q000494:pharmacology; D001570:Benzodiazepinones / Q000494:pharmacology; D002243:Carbolines / Q000378:metabolism / Q000494:pharmacology*; D004193:Discrimination Learning / Q000187:drug effects*; D005442:Flumazenil; D006632:Histamine / Q000494:pharmacology; D008253:Macaca mulatta; D008723:Methohexital / Q000008:administration & dosage; D008874:Midazolam; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology*
D001570:Benzodiazepinones; D002243:Carbolines; D011963:Receptors, GABA-A; D001569:Benzodiazepines; D005442:Flumazenil; C024915:beta-carboline-3-carboxylic acid ethyl ester; D006632:Histamine; D008723:Methohexital; D008874:Midazolam