Levodopa-induced dyskinesia (LID) is experienced by most patients of Parkinson’s disease (PD) upon the long-term use of the dopamine precursor levodopa. Striatal dopaminergic signaling plays a critical role in the pathogenesis of LID through its interactions with dopamine receptors. The specific roles of striatal dopaminergic D₅ receptors in the pathophysiological process of LID are still poorly established. In the study, we investigated the role of striatal dopamine D₅ receptor in LID by using PD rats with or without dyskinetic symptoms after chronic levodopa administration. The experimental results showed that the expression level of D₅ receptors in the sensorimotor striatum of dyskinetic rats is significantly higher than that of the non-dyskinetic controls. The administration of levodopa increased c-Fos expression in a subpopulation of sensorimotor striatum neurons of dyskinetic rats, but not in non-dyskinetic rats. The majority of the c-Fos⁺ neurons activated by levodopa in the striatum are positive for D₅ receptor staining. Intrastriatal injection of D₁-like (D₁ and D₅) dopamine receptor antagonist, SCH-23390, significantly inhibited dyskinetic behavior in dyskinetic rats after the injection of levodopa, meanwhile, intrastriatal administration of SKF-83959, a partial D₅ receptor agonist, yielded significant dyskinetic movements in dyskinetic rats without levodopa. In contrast, intrastriatal perfusion of small interfering RNA directed against DRD5 downregulated D₅ receptors expression and moderately inhibited dyskinetic behavior of dyskinetic animals. Our data suggested that the striatal dopamine D₅ receptor might play a novel role in the pathophysiology of LID.

大多数帕金森病（PD）患者在长期使用多巴胺前体左旋多巴后会出现左旋多巴诱发的运动障碍（LID）。纹状体多巴胺能信号通过其与多巴胺受体的相互作用在 LID 的发病机制中发挥着关键作用。纹状体多巴胺能 D ₅受体在 LID 病理生理过程中的具体作用仍不清楚。在这项研究中，我们通过使用慢性左旋多巴给药后有或没有运动障碍症状的PD大鼠，研究了纹状体多巴胺D ₅受体在LID中的作用。实验结果显示，运动障碍大鼠感觉运动纹状体中D ₅受体的表达水平显着高于非运动障碍对照。给予左旋多巴可增加运动障碍大鼠感觉运动纹状体神经元亚群中的 c-Fos 表达，但在非运动障碍大鼠中则不然。纹状体中由左旋多巴激活的大多数 c-Fos ⁺神经元的 D ₅受体染色呈阳性。纹状体内注射 D ₁样（D ₁和 D ₅ ）多巴胺受体拮抗剂 SCH-23390 可显着抑制注射左旋多巴后运动障碍大鼠的运动障碍行为，同时纹状体内注射部分 D ₅受体激动剂 SKF-83959 ，在没有左旋多巴的运动障碍大鼠中产生显着的运动障碍。相比之下，纹状体内灌注针对DRD5的小干扰RNA可下调D ₅受体表达并中度抑制运动障碍动物的运动障碍行为。 我们的数据表明纹状体多巴胺 D ₅受体可能在 LID 的病理生理学中发挥新的作用。