Ro 15-1788-induced seizures in rats continually exposed to diazepam for prolonged periods

Previous reports using rats have failed to demonstrate convulsions upon withdrawal from chronic benzodiazepine (BZ) treatment. We have shown earlier that rats develop tolerance to benzodiazepines following continuous exposure to low levels of diazepam (DZ) obtained by treatment with s.c. diazepam-filled silastic capsules. This report shows that intravenous infusion of the benzodiazepine antagonist Ro 15-1788 can induce seizures in rats treated for prolonged periods (4 weeks) with such diazepam-filled capsules. Precipitated seizures are also seen in rats 24 h after the cessation of chronic diazepam exposure. This procedure may provide a useful paradigm with which to study in rats the neural changes which are related to the physical dependence and withdrawal associated with prolonged exposure to the benzodiazepines.