Department of Neurology, Guangdong Province Hospital of Traditional Chinese Medical, Guangzhou 510120, China.
Department of Neurology, Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou 510370, China.
Ann Palliat Med. 2020 May;9(3):947-956. doi: 10.21037/apm.2020.03.32. Epub 2020 Apr 7.
Dyskinesia of rat models can occur in several conditions: acute levodopa (L-DOPA) administration provided that the drug dose is sufficiently high and/or that the nigrostriatal dopamine (DA) pathway is seriously damaged, and repeated L-DOPA administration which could cause a reduction of the dyskinesia-threshold dose, a progressive aggravation and an increasing incidence of dyskinesia. Therefore, if the damage of the nigrostriatal DA pathway is extremely severe, what abnormal movements can be elicited by first injecting L-DOPA or other dopaminergic agonists? The problem deserves exploring.
Rat models with damage of varying severity were divided into three groups: the serious lesion [induced by 40 µg 6-hydroxydopamine (6-OHDA), two injected coordinates including substantia nigra (SN) and medial forebrain bundle], the moderate lesion (20 µg 6-OHDA, a coordinate in SN) and the control. Three weeks after lesion, the Rota Rad test and Cylinder test were performed to assess the motor activities of rat models, the abnormal involuntary movements (AIMs) elicited by L-DOPA or apomorphine (APO) were observed, and the dopaminergic degeneration in SN and striatum was determined.
Both seriously lesioned rats and the moderately were observed to exhibit a significant decrease in motor activities. In the rats with a serious lesion, scarcely any dopaminergic neurons were present in the SN, tissue DA level decreased by 99% in the striatum, and both L-DOPA and APO could elicit AIMs and rotational movements. In the rats with the moderate lesion, only rotation movements could be elicited. The rotation speed of moderately lesioned rats was 9 turns/min, but that of seriously was only 4.5 turns/min elicited by APO.
Both dyskinesia and rotation movement are the specific expressions elicited by L-DOPA or APO in rats whose SN is damaged by 6-OHDA. Dyskinesia reflects more severe damage than rotation movement.
在几种情况下，大鼠模型会出现运动障碍：急性左旋多巴（L-DOPA）给药，只要药物剂量足够高和/或黑质纹状体多巴胺（DA）通路严重受损，以及重复的 L-DOPA 给药，可能导致运动障碍阈值剂量降低、逐渐加重和运动障碍发生率增加。因此，如果黑质纹状体 DA 通路的损伤极其严重，第一次注射 L-DOPA 或其他多巴胺激动剂会引起什么异常运动？这个问题值得探讨。
将损伤程度不同的大鼠模型分为三组：严重损伤[由 40μg 6-羟多巴胺（6-OHDA）诱导，两个注射坐标包括黑质（SN）和内侧前脑束]、中度损伤（20μg 6-OHDA，SN 中的一个坐标）和对照组。损伤后 3 周，进行转棒试验和圆筒试验评估大鼠模型的运动活动，观察 L-DOPA 或阿朴吗啡（APO）引起的异常不自主运动（AIMs），并测定 SN 和纹状体的多巴胺能变性。
严重损伤和中度损伤的大鼠均观察到运动活动明显减少。在严重损伤的大鼠中，SN 中几乎没有多巴胺能神经元，纹状体中的组织 DA 水平降低了 99%，L-DOPA 和 APO 均可引起 AIMs 和旋转运动。在中度损伤的大鼠中，仅可引起旋转运动。中度损伤大鼠的旋转速度为 9 转/分，而严重损伤大鼠的旋转速度仅为 4.5 转/分，由 APO 引起。
6-OHDA 损伤 SN 后，L-DOPA 或 APO 引起的运动障碍和旋转运动均为大鼠的特异性表现。运动障碍比旋转运动反映更严重的损伤。
