Dawson G.R., Heyes C.M., Iversen S.D.
Merck Sharp & Dohme Neuroscience Research Centre, Terlings Park, Harlow, Essex, UK.
Behav Pharmacol. 1992 Aug;3(4):285-297.
Requirements for an effective animal model of cognition are discussed with special reference to the cholinergic hypothesis of Alzheimer's disease. It is argued, with reference to research on vasopressin and ACE inhibitors, that many putative animal models of cognition lack predictive clinical validity because they either confound the effects of cognitive and arousal processes, or fail to model a specific component of cognitive functioning. A survey of recent research on the cholinergic hypothesis illustrates how these weaknesses can be overcome. Studies involving scopolamine and basal forebrain excitatory amino acid lesion models of the cholinergic deficit in Alzheimer's disease have employed a delayed-matching-to-position test in rodents which, unlike passive avoidance, allows the effects of memory and attentional variables to be distinguished. In combination with recent human studies, these experiments suggest that the cholinergic system has a major role in executive control of attentional resources, and lead to the recommendation of a 'top down' strategy in the investigation of neurochemical processes and pharmacological mechanisms underlying cognition.
本文特别参照阿尔茨海默病的胆碱能假说，讨论了有效认知动物模型的要求。参考血管加压素和血管紧张素转换酶抑制剂的研究，有人认为许多假定的认知动物模型缺乏预测临床有效性，因为它们要么混淆了认知和唤醒过程的影响，要么未能模拟认知功能的特定组成部分。对胆碱能假说近期研究的综述说明了如何克服这些弱点。涉及东莨菪碱和阿尔茨海默病胆碱能缺陷的基底前脑兴奋性氨基酸损伤模型的研究，在啮齿动物中采用了延迟位置匹配测试，与被动回避不同，该测试能区分记忆和注意力变量的影响。结合近期的人体研究，这些实验表明胆碱能系统在注意力资源的执行控制中起主要作用，并建议在研究认知背后的神经化学过程和药理机制时采用“自上而下”的策略。
