Herrera-Marschitz Mario, Bustamante Diego, Morales Paola, Goiny Michel
Programme of Molecular and Clinical Pharmacology, ICBM, Medical Faculty, University of Chile, Santiago, Chile.
Neurotox Res. 2007 Apr;11(3-4):169-82. doi: 10.1007/BF03033566.
The detailed anatomy of the monoamine pathways of the rat, first described by the students of Nils Ake Hillarp in Sweden, provided the basis for a neurocircuitry targeted pharmacology, leading to important therapeutic breakthroughs. Progress was achieved by the introduction of accurate lesion techniques based on selective neurotoxins. Systematic intracerebral injections of 6-hydroxydopamine let Urban Ungerstedt at the Karolinska Institutet, Stockholm, Sweden, to propose the first stereotaxic mapping of the monoamine pathways in the rat brain; and the 'Rotational Behaviour', as a classical model for screening drugs useful for alleviating Parkinson's disease and other neuropathologies. The direction of the rotational behaviour induced by drugs administrated to unilaterally 6-hydroxydopamine-lesioned rats reveals their mechanism of action at dopamine synapses, as demonstrated when rotational behaviour was combined with microdialysis. The model was useful for proposing a role for dopamine receptors in the gating of the flow of information integrated and/or modulated by the basal ganglia, through different efferent pathways; notably the striatopallidal system, via D(2) receptors, and the striatonigral system, via D(1) receptors. The role of other dopamine receptor subtypes on rotational behaviour has not yet been clarified.
大鼠单胺能通路的详细解剖结构最早由瑞典的尼尔斯·阿克·希拉尔普的学生描述，为神经回路靶向药理学提供了基础，从而带来了重要的治疗突破。通过引入基于选择性神经毒素的精确损伤技术取得了进展。瑞典斯德哥尔摩卡罗林斯卡学院的乌尔班·翁格尔斯泰德通过向大鼠脑内系统注射6-羟基多巴胺，提出了大鼠脑中单胺能通路的首个立体定位图谱；以及“旋转行为”，作为筛选对缓解帕金森病和其他神经病理学有用药物的经典模型。给单侧6-羟基多巴胺损伤的大鼠给药所诱导的旋转行为方向揭示了其在多巴胺突触处的作用机制，这在旋转行为与微透析相结合时得到了证明。该模型有助于提出多巴胺受体在基底神经节整合和/或调节的信息流通过不同传出通路（特别是通过D(2)受体的纹状体苍白球系统和通过D(1)受体的纹状体黑质系统）的门控中的作用。其他多巴胺受体亚型对旋转行为的作用尚未阐明。
