GABAA receptors in damaged cerebral cortex areas in human chronic alcoholics

Chronic alcoholics without complicating disease showed greater densities of GABA agonist sites (labelled with the selective ligand [3H]muscimol) on the GABAA receptor in the superior frontal gyrus, in comparison with both precentral gyrus in the same cases, and with superior frontal gyrus in matched controls. Whereas cases with concomitant Wernicke encephalopathy may also have had greater numbers of superior frontal [3H]muscimol binding sites than controls, alcoholics with cirrhosis of the liver showed more muted differences. Since the GABAA receptor is a multimeric complex which also possesses binding sites for "central-type" benzodiazepine ligands, it would be expected that data obtained with these compounds should mimic that obtained with [3H]muscimol. This was not so. [3H]Flunitrazepam binding sites showed little variation between case groups, although they showed clear regional differences. [3H]Diazepam sites followed those for [3H]muscimol in uncomplicated alcoholics and alcoholics with cirrhosis of the liver, but were at lower density in superior frontal gyrus in Wernicke cases. Differential expression of GABAA receptor subunit isoform genes may give rise to these disparities.