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

Gamma-aminobutyric acid (gaba) is an important inhibitory transmitter incentral nervous system and is involved in pathophysiology of epilepsy. pentylenetetrazole(ptz), a convulsant agent, partly acts via anion channel of gabaa receptor.ivermectin, an antiparasitic agent and a gabaa agonist, has anticonvulsant effectin animal seizure models. cholestasis increases the threshold of ptz-inducedclonic seizure in mice. the object of this study was to clarify the involvement ofgabaergic pathways in increasing ptz-induced seizure threshold (st) in cholestaticmice. the result of this study showed that cholestasis increases clonic st three daysafter 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-ligatedmice, respectively. in conclusion, our results showed that: (1) acute cholestasis isassociated with an increase in ptz-induced clonic st in mice and this phenomenonmay be the result of reinforcement of gabaergic system, and (2) gaba plays aphysiological role in regulation of st.