Tollefson G D, Gade J
Biol Psychiatry. 1983 Apr;18(4):481-91.
Neuropsychiatric impairment during senescence and consequent to alcohol abuse demonstrates several parallels in the areas of short-term memory and sensorimotor skills. In this study high-affinity binding of the muscarinic cholinergic antagonist quinuclidinyl benzilate (QNB) was determined with post-mortem human brain tissue from normal young adults, age-matched ethanol abusers, and nondemented senior adults without histories of substance abuse. Hippocampus was chosen because of its high-density cholinergic innervation and probable role in the mnemonic process. A statistical significance emerged between nonalcoholic young adults and both ethanol abusers and seniors in reference to cooperative binding interactions (Hill coefficient, nH) amongst the latter two groups. Analysis of the respective receptor affinities (KD) revealed a significant difference between each group. A trend toward an increased KD occurred from nonalcoholic young adults to alcoholic young adults to nonalcoholic seniors. Concerning the density of receptor sites (Bmax) no difference emerged between alcoholic or nonalcoholic young adults. However nonalcoholic seniors manifest a statistically significant reduction in Bmax; this feature is consistent with the reports of several other investigators. Amongst subjects with a pathologic history of ethanol abuse, a premature senescence along parameters of nH and KD emerged, albeit not including the apparent age-dependent decline in Bmax.
衰老过程中以及因酒精滥用导致的神经精神损伤在短期记忆和感觉运动技能方面表现出若干相似之处。在本研究中，使用来自正常年轻成年人、年龄匹配的乙醇滥用者以及无药物滥用史的非痴呆老年人的死后人类脑组织，测定了毒蕈碱胆碱能拮抗剂苄基喹宁环酯（QNB）的高亲和力结合。选择海马体是因为其高密度的胆碱能神经支配以及在记忆过程中可能发挥的作用。在非酒精性年轻成年人与乙醇滥用者及老年人之间，就后两组之间的协同结合相互作用（希尔系数，nH）而言，出现了统计学显著性差异。对各自受体亲和力（KD）的分析显示每组之间存在显著差异。从非酒精性年轻成年人到酒精性年轻成年人再到非酒精性老年人，KD有增加的趋势。关于受体位点密度（Bmax），酒精性或非酒精性年轻成年人之间未出现差异。然而，非酒精性老年人的Bmax在统计学上显著降低；这一特征与其他几位研究者的报告一致。在有乙醇滥用病理史的受试者中，沿着nH和KD参数出现了早衰现象，尽管不包括明显的与年龄相关的Bmax下降。
