RECEPTOR-BINDING SITES AND UPTAKE ACTIVITIES MEDIATING GABA NEUROTRANSMISSION IN CHRONIC-ALCOHOLICS WITH WERNICKE ENCEPHALOPATHY

Superior frontal cortex (SFC) and primary motor cortex tissue was obta ined at autopsy from thirteen severe chronic alcoholics with neuropath ologically confirmed Wernicke Encephalopathy (WE) and 22 controls. Cas es with both WE and cirrhosis showed markedly fewer neurones in SFC th an did WE cases without cirrhosis. The extent of the apparent neuronal loss corresponded to an increase in post-synaptic GABA(A) receptor si tes, as assessed by the binding of [H-3]muscimol to synaptic membranes . Increased [H-3]muscimol binding was not accompanied by an increase i n 'central-type' benzodiazepine binding sites: as assessed by [H-3]flu nitrazepam binding, these sites were apparently unaltered, while as as sessed by [H-3]diazepam binding, they were decreased. The affinities o f the two benzodiazepine ligands varied differently with disease. Thes e discrepancies between [H-3]flunitrazepam and [H-3]diazepam binding c ould not be accounted for, either by the presence of a second, diazepa m-preferring, 'central-type' benzodiazepine binding site, or by loss o f 'peripheral-type' sites. The changes in the post-synaptic GABA(A)-be nzodiazepine receptor sites did not reflect any regional, disease-rela ted deficit of afferent GABAergic terminals, as assessed by synaptosom al high-affinity [H-3]GABA uptake. On a number of indices, it appears most likely that the data reflect both a loss of receptor sites, and a change in the population of receptor sub-types.