Ro 15-1788, CGS 8216, Picrotoxin, and Pentylenetetrazol: Do They Antagonize Anxiolytic Drug Effects Through an Anxiogenic Action?

Recent evidence suggests that agents that inhibit GABAergic function, particularly at sites on the GABA/benzodiazepine receptor complex, have intrinsic anxiogenic properties. The present experiments further characterize the behavioral effects of these receptor complex inhibitors, using the "defensive burying" test, which is reasonably selective for anxiolytics. Putative blockers of the GABA-receptor coupled chloride channel, picrotoxin and pentylenetetrazol, and the benzodiazepine receptor antagonists Ro 15-1788 and CGS 8216 each blocked the anxiolytic effect of chlordiazepoxide. However, these compounds failed to exert significant anxiogenic effects in the burying test. These findings suggest that different animal models of anxiolytic drug effects are not equally sensitive to the possible anxiogenic effects of drugs that act at the GABA/benzodiazepine receptor complex.