Involvement of GABAergic System in Increased Pentylenetetrazole-Induced Seizure Threshold in Cholestatic Mice

Abstract

Gamma-aminobutyric acid (GABA) is an important inhibitory transmitter in central nervous system and is involved in pathophysiology of epilepsy. Pentylenete-trazole (PTZ), a convulsant agent, partly acts via anion channel of GABA_A receptor. Ivermectin, an antiparasitic agent and a GABA_A agonist, has anticonvulsant effect in animal seizure models. Cholestasis increases the threshold of PTZ-induced clonic seizure in mice. The object of this study was to clarify the involvement of GABAergic pathways in increasing PTZ-induced seizure threshold (ST) in cholestatic mice. The result of this study showed that cholestasis increases clonic ST three days after surgery while sham-operated control (SOC) and unoperated control (UOC) groups did not show any alteration in clonic ST. Bicuculline, a GABA_A antagonist, reversed but ivermectin increased the clonic ST in UOC, SOC and bile duct-ligated mice, respectively. In conclusion, our results showed that: (1) acute cholestasis is associated with an increase in PTZ-induced clonic ST in mice and this phenomenon may be the result of reinforcement of GABAergic system, and (2) GABA plays a physiological role in regulation of ST.