Effects of repeated RO 15-1788 administration in benzodiazepine-dependent baboons

Administration of the benzodiazepine antagonist, RO 15-1788, to baboons that were chronically exposed to diazepam or triazolam precipitated withdrawal signs. When RO 15-1788 was administered repeatedly at one or three day intervals, precipitated withdrawal signs were attenuated. However, these baboons remained tolerant to the sedative effects of the high doses of benzodiazepines to which they were continuously exposed. While tolerance to agonist effects of drugs and development of physical dependence are often thought to be functionally interrelated phenomena, the present results suggest that these may be separable properties of the benzodiazepines. The present results clearly indicate that certain actions of benzodiazepine agonists and antagonists can be independently regulated.