研究人类和动物模型并行行为的持续挑战。

Q3 Neuroscience
Hans S Crombag, Theodora Duka, David N Stephens
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引用次数: 0

摘要

使用动物模型对于开展包括成瘾在内的临床现象研究仍然至关重要。然而,临床症状的复杂性不可避免地意味着即使是最好的动物模型也是不够的,这可能在某种程度上解释了为什么动物模型的发现,包括潜在新疗法的鉴定,显然未能转化到临床。我们在此认为,试图用动物,尤其是啮齿类动物来模拟复杂、多方面的人类疾病(如成瘾)首先是好高骛远和误入歧途,而且这类模型的 "有效性 "往往局限于表面的相似性,即所谓的 "表面有效性",而这些相似性所反映的潜在现象和生物过程与临床情况大相径庭。相反,更有效的方法是确定:(a) 明确界定的中间人类行为表型,这些表型反映了人类临床失调症的明确、有限的方面或促成因素;(b) 建立在心理过程和潜在神经生物学机制方面与这些离散人类行为表型同源的动物模型。本文举例说明了过去和现在的不足之处,并建议采用更有限的方法,使试验动物和人类状况之间具有更好的同源性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The Continuing Challenges of Studying Parallel Behaviours in Humans and Animal Models.

The use of animal models continues to be essential for carrying out research into clinical phenomena, including addiction. However, the complexity of the clinical condition inevitably means that even the best animal models are inadequate, and this may go some way to account for the apparent failures of discoveries from animal models, including the identification of potential novel therapies, to translate to the clinic. We argue here that it is overambitious and misguided in the first place to attempt to model complex, multifacetted human disorders such as addiction in animals, and especially in rodents, and that all too frequently "validity" of such models is limited to superficial similarities, referred to as "face validity", that reflect quite different underlying phenomena and biological processes from the clinical situation. Instead, a more profitable approach is to identify (a) well-defined intermediate human behavioural phenotypes that reflect defined, limited aspects of, or contributors to, the human clinical disorder, and (b) to develop animal models that are homologous with those discrete human behavioural phenotypes in terms of psychological processes, and underlying neurobiological mechanisms. Examples of past and continuing weaknesses and suggestions for more limited approaches that may allow better homology between the test animal and human condition are made.

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来源期刊
Current topics in behavioral neurosciences
Current topics in behavioral neurosciences Neuroscience-Behavioral Neuroscience
CiteScore
4.80
自引率
0.00%
发文量
103
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