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东莨菪碱对人类受试者视觉记忆和学习的延迟匹配样本及配对联想测试的影响:与地西泮的比较及对痴呆症的意义

Effects of scopolamine on delayed-matching-to-sample and paired associates tests of visual memory and learning in human subjects: comparison with diazepam and implications for dementia.

作者信息

Robbins T W, Semple J, Kumar R, Truman M I, Shorter J, Ferraro A, Fox B, McKay G, Matthews K

机构信息

Department of Experimental Psychology, University of Cambridge, UK.

出版信息

Psychopharmacology (Berl). 1997 Nov;134(1):95-106. doi: 10.1007/s002130050430.

DOI:10.1007/s002130050430
PMID:9399372
Abstract

Two experiments examined dose-related effects of 200, 400 and 600 micrograms scopolamine (n = 24, s.c.) and 5 and 10 mg diazepam (n = 6, PO) on parallel tests of visual memory and learning taken from the CANTAB battery. Scopolamine significantly impaired accuracy of performance on a delayed matching to sample test of visual recognition memory in a dose- and delay-dependent manner, but had only marginal decremental effects on a test of visuospatial paired associates learning. Scopolamine significantly lengthened decision times in a visual search matching to sample task at the 400 and 600 micrograms doses, without significantly affecting accuracy. The drug also impaired performance on tests of spatial (on accuracy and response time measures) and pattern (on response time only) memory. Most of the deleterious effects on scopolamine were removed by covariance analyses with indices of subjective sedation, but the effects of delayed matching accuracy and latency remained. By contrast, diazepam significantly impaired paired associates learning but affected delayed matching to sample in a delay-independent manner. These results suggest that scopolamine can produce selective deficits in tests of short-term visual recognition memory which do not depend on overall impairments in arousal and which contrast with deficits in visual associative learning produced by diazepam. They have implications for the pharmacological modelling of dementia and memory disorders in man and for the neurochemical substrates of the short-term recognition memory and associative learning for visual stimuli.

摘要

两项实验研究了200、400和600微克东莨菪碱(皮下注射,n = 24)以及5和10毫克地西泮(口服,n = 6)对取自剑桥神经心理测试自动化成套系统(CANTAB)的视觉记忆和学习平行测试的剂量相关效应。东莨菪碱以剂量和延迟依赖的方式显著损害了视觉识别记忆的延迟样本匹配测试中的表现准确性,但对视觉空间配对联想学习测试只有轻微的递减效应。在400和600微克剂量下,东莨菪碱显著延长了视觉搜索样本匹配任务中的决策时间,而没有显著影响准确性。该药物还损害了空间(准确性和反应时间测量)和模式(仅反应时间)记忆测试中的表现。通过与主观镇静指标进行协方差分析,消除了东莨菪碱的大部分有害影响,但延迟匹配准确性和潜伏期的影响仍然存在。相比之下,地西泮显著损害了配对联想学习,但以与延迟无关的方式影响了延迟样本匹配。这些结果表明,东莨菪碱可在短期视觉识别记忆测试中产生选择性缺陷,这些缺陷不依赖于整体觉醒障碍,且与地西泮所致的视觉联想学习缺陷形成对比。它们对人类痴呆和记忆障碍的药理学模型以及视觉刺激的短期识别记忆和联想学习的神经化学底物具有启示意义。

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