Broks P, Preston G C, Traub M, Poppleton P, Ward C, Stahl S M
Neuroscience Research Centre, Merck Sharp & Dohme Research Laboratories, Harlow, Essex, U.K.
Neuropsychologia. 1988;26(5):685-700. doi: 10.1016/0028-3932(88)90004-8.
Scopolamine, a muscarinic cholinergic antagonist, is capable of inducing transient memory impairment in normal subjects. Against the background of the cholinergic hypothesis of Alzheimer's disease (AD) the present study was designed to investigate the effects of low oral doses of scopolamine on a range of cognitive functions known or hypothesized to be affected in AD. Twenty healthy volunteers (18-48 yr) performed a battery of automated cognitive tasks under each of five treatments: oral scopolamine 0.3 mg, 0.6 mg, 1.2 mg; oral methylscopolamine 0.6 mg; placebo. Alongside analogous tests of verbal and non-verbal memory, the battery enabled assessments of a range of attentional functions: alerting, sustained attention, selective attention, and covert orientation. A profile of effects was observed within and beyond the realm of memory. While some functions were unaffected by the drug (e.g. alerting) and others were impaired at the highest dose (e.g. verbal learning) still others were affected in a linear dose-dependent manner (sustained attention; visual contrast sensitivity). These observations are discussed in the context of the "scopolamine model" of AD.
东莨菪碱是一种毒蕈碱胆碱能拮抗剂,能够在正常受试者中诱发短暂性记忆障碍。在阿尔茨海默病(AD)胆碱能假说的背景下,本研究旨在调查低口服剂量东莨菪碱对一系列已知或被认为在AD中受影响的认知功能的作用。20名健康志愿者(18 - 48岁)在以下五种治疗方式下分别进行了一系列自动化认知任务:口服0.3毫克、0.6毫克、1.2毫克东莨菪碱;口服0.6毫克甲基东莨菪碱;安慰剂。除了类似的言语和非言语记忆测试外,该系列测试还能够评估一系列注意力功能:警觉性、持续注意力、选择性注意力和隐蔽定向。在记忆领域内外均观察到了一系列效应。虽然有些功能不受药物影响(如警觉性),有些功能在最高剂量时受损(如言语学习),但其他一些功能则呈线性剂量依赖性受到影响(持续注意力;视觉对比敏感度)。将结合AD的“东莨菪碱模型”对这些观察结果进行讨论。