Cyclothiazide induces seizure behavior in freely moving rats.
We have previously demonstrated that cyclothiazide (CTZ) is a potent convulsant drug inducing robust epileptiform 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 3h after administration. At a dose of 0.75 μmol, 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.
Kong
Shuzhen
S
Research Centre of Medicinal Chemistry and Chemical Biology, Chongqing Technology and Business University, Chongqing, China.
Qian
Binbin
B
Liu
Jianhui
J
Fan
Mingxin
M
Chen
Gong
G
Wang
Yun
Y
D000818:Animals; D000959:Antihypertensive Agents / Q000037:antagonists & inhibitors / Q000633:toxicity; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology; D001581:Benzothiadiazines / Q000037:antagonists & inhibitors / Q000633:toxicity*; D001921:Brain / Q000187:drug effects* / Q000503:physiopathology; D003292:Convulsants / Q000037:antagonists & inhibitors / Q000633:toxicity*; D004195:Disease Models, Animal; D004827:Epilepsy / Q000139:chemically induced* / Q000503:physiopathology*; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology; D008297:Male; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley
D000959:Antihypertensive Agents; D001581:Benzothiadiazines; D003292:Convulsants; C004639:cyclothiazide