title: Hepatic encephalopathy, GABA-ergic neurotransmission and benzodiazepine receptor ligands.
abstract: Evidence compatible with increased GABAergic tone contributing to the manifestations of hepatic encephalopathy (HE) in animal models of fulminant hepatic failure (FHF) includes: (i) increased resistance to drugs which induce seizures by reducing GABAergic tone; (ii) abnormalities of visual evoked responses (VERs) which resemble those induced by drugs which augment GABAergic tone; (iii) increased sensitivity of CNS neurons to a GABA agonist; and (iv) ameliorations of the encephalopathy induced by a GABA receptor antagonist. Evidence compatible with a benzodiazepine (BZ) receptor ligand with agonist properties contributing to increased GABAergic tone in animal models of FHF includes: (i) abnormalities of VERs which resemble those in BZ agonist-induced coma; (ii) increased sensitivity of CNS neurons to a BZ receptor agonist; (iii) excitation of CNS neurons induced by BZ receptor antagonists; (iv) reversal of the increased sensitivity of CNS neurons to a GABA agonist by a BZ receptor antagonist; (v) presence of a ligand(s) in brain which displaces a radiolabeled ligand from BZ receptors; and (vi) increased affinity of this ligand(s) for BZ receptors in the presence of GABA ("positive GABA shift").
authors.affiliation: Liver Diseases Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland.
authors.forename: E A
authors.initials: EA
authors.lastname: Jones
authors.forename: A S
authors.initials: AS
authors.lastname: Basile
authors.forename: P
authors.initials: P
authors.lastname: Skolnick
mesh_terms: D000818:Animals; D006501:Hepatic Encephalopathy / Q000503:physiopathology*; D006801:Humans; D008024:Ligands; D011963:Receptors, GABA-A / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
chemical_list: D008024:Ligands; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid