Although extrastriatal dopaminergic (DAergic) systems are being recognized as contributors to Parkinson's disease (PD) pathophysiology, the role of extrastriatal DA depletion in L-Dopa-induced dyskinesia (LID) is still unknown. In view of the physiologic actions of DA on pallidal neuronal activity and the effects on motor behavior of local injection of DA drugs, the loss of the external (GPe, GP in rodents) and internal (GPi, entopeduncular nucleus (EP) in rodents) pallidal DAergic innervation might differentially contribute to LID. A role of pallidal serotonergic (SER) terminals in LID has been highlighted, however, the effect of DAergic innervation is unknown.

We investigated the role of DAergic pallidal depletion on LID. Rats were distributed in groups which were concomitantly lesioned with 6-OHDA or vehicle (sham) in the GP, or EP, and in the medial forebrain bundle (MFB) as follows: a) MFB-sham+GP-sham, b) MFB-sham+GP-lesion, c) MFB-lesion+GP-sham, d) MFB-lesion+GP-lesion, e) MFB-sham+EP-sham, f) MFB-sham+EP-lesion, g) MFB-lesion+EP-sham, and h) MFB-lesion+EP-lesion. Four weeks later, animals were treated with L-Dopa (6 mg/kg) twice daily for 22 days.. Immunohistochemical studies were performed in order to investigate the changes in pallidal SER and serotonin transporter (SERT) levels.

GP, but not EP, DAergic denervation attenuated LID in rats with a concomitant MFB lesion (p < 0.01). No differences were found in GP SERT expression between groups of animals developing or not LID.

These results provide evidence of the relevance of GP DAergic innervation in LID. The conversion of levodopa to DA in GP serotonergic nerve fibers appears not to be the major mechanism underlying LID.

尽管纹状体多巴胺能（DAergic）系统被认为是帕金森氏病（PD）病理生理的原因，但纹状体多巴胺耗竭在左旋多巴诱发的运动障碍（LID）中的作用仍是未知的。鉴于DA对苍白神经元活动的生理作用以及局部注射DA药物对运动行为的影响，外在（啮齿类动物的GPe，GP）和内部（GPi，啮齿类动物的上皮核（EP））的丧失苍白DA的神经支配可能对LID有不同的贡献。苍白的血清素能（SER）末端在LID中的作用已得到强调，但是，DA能神经支配的作用尚不清楚。

我们调查了DAergic苍白层耗竭对LID的作用。将大鼠分成在GP或EP和前脑内侧束（MFB）中伴有6-OHDA或媒介物（假手术）的病变组，如下所示：a）MFB假手术+ GP-假手术，b）MFB -sham + GP-病变，c）MFB-病变+ GP-sham，d）MFB-病变+ GP-病变，e）MFB-sham + EP-sham，f）MFB-sham + EP-病变，g）MFB -病变+ EP假手术，以及h）MFB病变+ EP病变。四周后，每天两次用L-Dopa（6 mg / kg）治疗动物，持续22天。进行免疫组织化学研究，以研究苍白SER和血清素转运蛋白（SERT）水平的变化。

GP，但不是EP，DA能神经去神经作用可减轻MFB病变伴发大鼠的LID（p  <0.01）。在没有发育或没有LID的动物组之间，GP SERT表达没有发现差异。

这些结果提供了LID中GP DA能神经支配的相关证据。左旋多巴转化为GP血清神经营养神经纤维中的DA似乎不是LID的主要机制。