involvement of gabaergic system in increased pentylenetetrazole-induced seizure threshold in cholestatic mice

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 gabaa receptor. ivermectin, an antiparasitic agent and a gabaa 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 gabaa 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.