Binding of benzodiazepine recognition sites by various ligands can elicit opposite types of responses, such as proconvulsant/anticonvulsant, or anxiogenic/anxiolytic. In order to answer whether a new class of drugs belong to benzodiazepine (anxiolytic) or beta-carboline (anxiogenic) type of ligands we developed a behavioral animal model that predicts the anxiogenic and anxiolytic potency of a drug. In this test the imidarobenzodiazepine, RO 15 1788 acts like an inert antagonist of both beta-carboline like or benzodiazepine like drugs. However, in animals in which GABAergic transmission is reduced by the administration of small doses of the glutamic acid decarboxylase inhibitor isoniazid, RO 15 1788 became a weak beta carboline like agent. These data suggest that multiple chemical signals are operative in the expression of GABAergic transmission and that full understanding of this multiplicity require pharmacological manipulation at GABAergic synapses.
