Dodd P R
John Wilson Memorial Clinical Research Laboratory, Royal Brisbane Hospital Foundation, Bancroft Centre, Herston, Queensland, Australia.
Alcohol Alcohol Suppl. 1994;2:187-91.
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.
无并发症的慢性酗酒者，与同一病例的中央前回以及匹配对照组的额上回相比，其额上回GABAA受体上GABA激动剂位点（用选择性配体[3H]蝇蕈醇标记）的密度更高。虽然伴有韦尼克脑病的病例其额上回[3H]蝇蕈醇结合位点数量可能也比对照组多，但肝硬化酗酒者的差异则不太明显。由于GABAA受体是一种多聚体复合物，也拥有“中枢型”苯二氮䓬配体的结合位点，因此预期用这些化合物获得的数据应与用[3H]蝇蕈醇获得的数据相似。但实际并非如此。[3H]氟硝西泮结合位点在病例组之间变化不大，尽管它们显示出明显的区域差异。[3H]地西泮位点在无并发症酗酒者和肝硬化酗酒者中与[3H]蝇蕈醇位点的变化趋势一致，但在韦尼克病例的额上回中密度较低。GABAA受体亚基同工型基因的差异表达可能导致了这些差异。
