Sanger D J, Joly D
Laboratoires d'Etudes et de Recherches Synthélabo, Bagneux, France.
Pharmacopsychiatry. 1990 Feb;23 Suppl 2:70-4. doi: 10.1055/s-2007-1014537.
In order to discover and develop drugs to treat cognitive decline, animal tests are needed which will predict clinical activity. The process of developing such animal models does not differ, in principle, from the approaches used in other areas of psychotropic drug research. One research approach involves attempts to create models homologous with the disorder to be treated. This requires a thorough analysis of the clinical problem and an attempt to reproduce the biological and behavioral aspects of the disorder in animals. Recent studies of the effects of certain brain lesions on learning in monkeys or rats as models of Alzheimer's disease may go some way towards developing an animal model for this disorder. However, it is arguable whether this approach to "modelling" has ever had much success in psychopharmacology. A more pragmatic strategy involves the development of what are sometimes called emperical models, according to which any biological and behavioral test can be used if it provides a reasonable prediction of activity in the clinic. For example, the much used passive avoidance test in rodents does not need to model human cognition if it accurately predicts clinical activity. The extent to which this approach can be used successfully for evaluating cognition-enhancing drugs is discussed in view of the many drugs already marketed as cognition enhancers.
为了发现和开发治疗认知衰退的药物，需要进行动物试验，以预测临床活性。开发此类动物模型的过程，原则上与精神药物研究其他领域所采用的方法并无不同。一种研究方法是尝试创建与待治疗疾病同源的模型。这需要对临床问题进行透彻分析，并试图在动物身上重现该疾病的生物学和行为学方面。最近关于某些脑损伤对猴子或大鼠学习影响的研究，作为阿尔茨海默病的模型，可能在一定程度上有助于开发针对该疾病的动物模型。然而，这种“建模”方法在精神药理学中是否曾取得很大成功，是有争议的。一种更务实的策略是开发有时被称为经验模型的方法，根据这种方法，任何生物学和行为学测试，只要能合理预测临床活性，都可以使用。例如，如果啮齿动物中常用的被动回避测试能准确预测临床活性，就无需模拟人类认知。鉴于已有许多药物作为认知增强剂上市，本文讨论了这种方法在评估认知增强药物方面能够成功应用的程度。
