Cyclothiazide induces seizure behavior in freely moving rats

We have previously demonstrated that cyclothiazide (CTZ) is a potent convulsant drug inducing robust epileptiforrn activity in hippocampal neurons both in vitro and in vivo. Here we further establish an animal model for CTZ-induced behavioral seizures in freely moving rats. Microinjection of CTZ into the left ventricle dose-dependently induced robust seizure behaviors within 3 h after administration. At a dose of 0.75 mu mol, CTZ induced Racine score IV-V seizure behaviors in 71% (n=14) of the rats were tested. In addition, CTZ also induced epileptiform EEG activity accompanying behavioral seizures. The convulsant action of CTZ on both behavior and EEG was blocked by pretreatment with clinical anticonvulsant drug diazepam (n=5). In conclusion, our results demonstrate that CTZ is capable of inducing behavioral seizures in intact animals. Since CTZ acts on both GABAergic and glutamatergic systems, this new animal epilepsy model will be useful for anticonvulsant drug testing and general epilepsy research. (C) 2010 Elsevier B.V. All rights reserved.