RESISTANCE TO 3-MERCAPTOPROPIONIC ACID-INDUCED SEIZURES IN HEPATIC-ENCEPHALOPATHY

Background/Aims: To determine if a model of hepatic encephalopathy (HE ) exhibits decreased sensitivity to the neuronal effects of a drug tha t induces seizures as a consequence of decreasing GABA-mediated inhibi tory neurotransmission. Materials and Methods: 3-Mercaptopropionic Aci d (MPA) is an inhibitor of L-glutamate decarboxylase which catalyzes t he synthesis of GABA from glutamate. MPA was administered either by in traperitoneal or intracerebroventricular injection, into rats with sta ge III HE due to thioacetamide-induced fulminant hepatic failure and i nto normal control rats. Results: When MPA was administered by intrape ritoneal injection, seizure-inducing doses were similar for rats with HE and control rats. However, when a constant dose of MPA (330 mu g) w as administered by intracerebroventricular injection, rats with HE too k significantly longer to develop seizures than control rats (16.2 vs. 7.3 minutes; p < 0.0005). Conclusions: In a model of HE: (i) There is increased resistance to the convulsive effects of MPA; and (ii) This phenomenon is apparent when MPA is given centrally, but not when it is given peripherally. Increased resistance to the development of a comp lication of reduced GABA-mediated neurotransmission. induced by MPA in the model provides support for the hypothesis that HE is associated w ith increased GABA-mediated inhibitory neurotransmission.