Autoradiographic analysis of GABA-benzodiazepine receptors in an animal model of acute hepatic encephalopathy.
To complement analogous studies using conventional ligand-membrane binding assays, the densities of gamma-aminobutyric acid and benzodiazepine receptors in the brain have been assessed using an autoradiographic technique in an animal model of hepatic encephalopathy. Hepatic encephalopathy due to fulminant hepatic failure was induced in rabbits by the intravenous injection of galactosamine. The specific binding of three radiolabeled ligands was assessed densitometrically in several microregions of cerebral cortex, hippocampus and cerebellum. [3H]Muscimol was used to assess gamma-aminobutyric acid receptor density and [3H]flunitrazepam or [3H]Ro 15-1788 was used to assess benzodiazepine receptor density. No significant differences were observed between the magnitude of binding of the three ligands to each of the microregions of brain from control rabbits and rabbits in Stage III or IV hepatic encephalopathy. These findings suggest that the behavioral expression of hepatic encephalopathy in the model studied is not dependent upon an increase in the number of gamma-aminobutyric acid or benzodiazepine receptors, but do not conflict with the hypothesis that gamma-aminobutyric acid-ergic tone is increased in hepatic encephalopathy.
Rössle
M
M
Liver Diseases Section, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland 20892.
Deckert
J
J
Jones
E A
EA
D000208:Acute Disease; D000818:Animals; D001345:Autoradiography; D001923:Brain Chemistry; D002531:Cerebellum / Q000032:analysis; D002540:Cerebral Cortex / Q000032:analysis; D004195:Disease Models, Animal; D006501:Hepatic Encephalopathy; D006624:Hippocampus / Q000032:analysis; D008297:Male; D011817:Rabbits; D011963:Receptors, GABA-A / Q000032:analysis*
D011963:Receptors, GABA-A