INTERACTIONS BETWEEN THE BENZODIAZEPINE RECEPTOR ANTAGONIST RO 15-1788 (FLUMAZEPIL) AND THE INVERSE AGONIST-BETA-CCE - BEHAVIORAL-STUDIES WITH SQUIRREL-MONKEYS

The effects of Ro 15-1788 and ethyl-.beta.-carboline-3-carboxylate (.beta.-CCE) were studied alone and in combination on the behavioral performances of squirrel monkeys. Under one procedure, performances maintained by food were suppressed by electric shock presentation (punishment or "conflict" procedure). Under a 2nd procedure, responding was maintained either by food or electric shock delivery under a 5 min fixed-interval schedule. Doses of .beta.-CCE between 0.1 and 3.0 mg/kg, i.m., produced graded decreases in punished responding which were reversed by pretreatment with Ro 15-1788 (1.0-10.0 mg/kg, i.m.). Low doses of .beta.-CCE (0.03-0.3 mg/kg, i.m.) increased responding of monkeys maintained by shock presentation, but did not affect food-maintained responding; higher doses of .beta.-CCE decreased responding under both schedules. These effects of .beta.-CCE are opposite those produced by the benzodiazepines under this procedure. Ro 15-1788 (1.0 mg/kg i.m.) antagonized the effects of .beta.-CCE, producing a shift to the right in the dose-response curves. Apparently, .beta.-CCE and Ro 15-1788 produce effects mediated by the same benzodiazepine receptor recognition site.