Peng Qiwei, Zhong Shaoping, Tan Yang, Zeng WeiQi, Wang Ji, Cheng Chi, Yang Xiaoman, Wu Yi, Cao Xuebing, Xu Yan
Department of Neurology, Tongji Medical College, Union Hospital, Huazhong University of Science and Technology, Wuhan, China.
Front Neurol. 2019 Oct 11;10:1016. doi: 10.3389/fneur.2019.01016. eCollection 2019.
Dyskinesia, a major motor complication resulting from dopamine replacement treatment, manifests as involuntary hyperkinetic or dystonic movements. This condition poses a challenge to the treatment of Parkinson's disease. So far, several behavioral models based on rodent with dyskinesia have been established. These models have provided an important platform for evaluating the curative effect of drugs at the preclinical research level over the past two decades. However, there are differences in the modeling and behavioral testing procedures among various laboratories that adversely affect the rat and mouse models as credible experimental tools in this field. This article systematically reviews the history, the pros and cons, and the controversies surrounding rodent models of dyskinesia as well as their behavioral assessment protocols. A summary of factors that influence the behavioral assessment in the rodent dyskinesia models is also presented, including the degree of dopamine denervation, stereotaxic lesion sites, drug regimen, monitoring styles, priming effect, and individual and strain differences. Besides, recent breakthroughs like the genetic mouse models and the bilateral intoxication models for dyskinesia are also discussed.
异动症是多巴胺替代治疗导致的一种主要运动并发症,表现为不自主的运动亢进或张力障碍性运动。这种情况给帕金森病的治疗带来了挑战。到目前为止,已经建立了几种基于患有异动症的啮齿动物的行为模型。在过去二十年中,这些模型为在临床前研究水平评估药物疗效提供了重要平台。然而,各个实验室在建模和行为测试程序方面存在差异,这对大鼠和小鼠模型作为该领域可靠的实验工具产生了不利影响。本文系统回顾了异动症啮齿动物模型的历史、优缺点、相关争议以及它们的行为评估方案。还介绍了影响啮齿动物异动症模型行为评估的因素总结,包括多巴胺去神经支配程度、立体定位损伤部位、药物方案、监测方式、启动效应以及个体和品系差异。此外,还讨论了异动症的基因小鼠模型和双侧中毒模型等近期突破。