First Hospital of Soochow University, Suzhou City, China.
Neurodegener Dis. 2012;9(1):11-7. doi: 10.1159/000328816. Epub 2011 Aug 26.
The development of abnormal involuntary movements or dyskinesia is a serious complication of L-3,4-dihydroxyphenylalanine (L-DOPA) therapy for Parkinson's disease (PD).
To evaluate the correlation between dopamine transporter (DAT) regulated by L-DOPA and the pathogenesis of dyskinesia in PD rats.
Thirty rats were used to establish the PD model by injecting 6-hydroxydopamine into the right medial forebrain bundle. The sham surgery rats (n = 4) received 4 μl of physiological saline. Then, 19 rats in which PD has been successfully induced were randomly assigned to the L-DOPA (20 mg/kg/day; n = 15) or model (saline; n = 4) group. After 4 weeks of treatment, (131)I-N-(3-fluoropropyl)-2β-carbomethoxy-3 β-(4-iodophenyl)nortropane was injected into the rats, and images of DAT in the brain were acquired using a storage phosphor plate. The levels of DAT-specific radioactivity uptake in the bilateral corpora striata (left/right) were compared.
There was no difference in DAT-specific radioactivity uptake between the bilateral corpora striata in the sham surgery rats. The images were clear and symmetrically distributed in the corpora striata. In PD model rats, the DAT-specific radioactivity uptake decreased on the lesioned side and the ratios of uptake between the corpora striata were increased. Accumulation of the radioligand on the lesioned side was sparse. In the L-DOPA group, the average ratio values were significantly increased in dyskinetic rats and reduced in nondyskinetic rats. In addition, the differences between the bilateral corpora striata were reduced in nondyskinetic rats.
L-DOPA was shown to downregulate DAT in some PD model rats. That process may be involved in the pathogenesis of dyskinesia.
左旋多巴（L-DOPA）治疗帕金森病（PD）可引起异常不自主运动或运动障碍等严重并发症。
评价 PD 大鼠纹状体多巴胺转运体（DAT）受 L-DOPA 调节与运动障碍发病的关系。
采用立体定向微量注射法将 6-羟多巴胺注入大鼠右侧中脑导水管周围灰质建立 PD 模型，假手术组（n=4）注入 4μl 生理盐水。成功建立 PD 模型的大鼠 19 只，随机分为 L-DOPA 组（20mg/kg/d，n=15）和模型组（生理盐水，n=4）。治疗 4 周后，用（131）I-N-（3-氟丙基）-2β-羰甲氧基-3β-（4-碘苯基）-n-托烷（（131）I-FP-CIT）进行 DAT 显像，用磷屏采集脑 DAT 图像，比较双侧纹状体 DAT 特异性放射性摄取比值（左/右）。
假手术组大鼠双侧纹状体 DAT 特异性放射性摄取比值无差异，DAT 显像清晰，纹状体分布对称。PD 模型组大鼠患侧纹状体 DAT 特异性放射性摄取比值降低，两侧比值增高，放射性配体在患侧浓聚稀疏。L-DOPA 组运动障碍大鼠平均比值显著增高，无运动障碍大鼠比值降低，且两侧比值差异减小。
L-DOPA 可下调部分 PD 模型大鼠纹状体 DAT，该过程可能与运动障碍的发病机制有关。
