Cenci M A, Lindgren H S
Basal Ganglia Pathophysiology Unit, Department of Experimental Medical Science, Lund University, S-221 84 Lund, Sweden.
Curr Opin Neurobiol. 2007 Dec;17(6):665-71. doi: 10.1016/j.conb.2008.01.004. Epub 2008 Mar 4.
The crucial role of dopamine (DA) in movement control is illustrated by the spectrum of motor disorders caused by either a deficiency or a hyperactivity of dopaminergic transmission in the basal ganglia. The degeneration of nigrostriatal DA neurons in Parkinson's disease causes poverty and slowness of movement. These symptoms are greatly improved by pharmacological DA replacement with L-3,4-dihydroxy-phenylalanine (L-DOPA), which however causes excessive involuntary movements in a majority of patients. L-DOPA-induced dyskinesia (abnormal involuntary movements) provides a topic of investigation at the interface between clinical and basic neuroscience. In this article, we review recent studies in rodent models, which have uncovered two principal alterations at the basis of the movement disorder, namely, an abnormal pre-synaptic handling of exogenous L-DOPA, and a hyper-reactive post-synaptic response to DA. Dysregulated nigrostriatal DA transmission causes secondary alterations in a variety of non-dopaminergic transmitter systems, the manipulation of which modulates dyskinesia through mechanisms that are presently unclear. Further research on L-DOPA-induced dyskinesia will contribute to a deeper understanding of the functional interplay between neurotransmitters and neuromodulators in the motor circuits of the basal ganglia.
多巴胺（DA）在运动控制中的关键作用体现在基底神经节中多巴胺能传递不足或亢进所引发的一系列运动障碍上。帕金森病中黑质纹状体多巴胺能神经元的退化导致运动减少和迟缓。通过用L-3,4-二羟基苯丙氨酸（L-DOPA）进行药理学多巴胺替代，这些症状可得到显著改善，然而，这会在大多数患者中引发过度的不自主运动。L-DOPA诱导的运动障碍（异常不自主运动）为临床神经科学与基础神经科学的交叉研究提供了一个课题。在本文中，我们综述了啮齿动物模型的近期研究，这些研究揭示了运动障碍背后的两个主要改变，即对外源性L-DOPA的突触前处理异常，以及对多巴胺的突触后反应过度活跃。黑质纹状体多巴胺传递失调会导致多种非多巴胺能递质系统的继发性改变，目前尚不清楚其通过何种机制调节运动障碍。对L-DOPA诱导的运动障碍的进一步研究将有助于更深入地理解基底神经节运动回路中神经递质和神经调质之间的功能相互作用。
