Aubert Incarnation, Guigoni Céline, Håkansson Kerstin, Li Qin, Dovero Sandra, Barthe Nicole, Bioulac Bernard H, Gross Christian E, Fisone Gilberto, Bloch Bertrand, Bezard Erwan
Centre National de la Recherche Scientifique Unite Mixte de Recherche 5541, Bordeaux Cedex, France.
Ann Neurol. 2005 Jan;57(1):17-26. doi: 10.1002/ana.20296.
Involuntary movements, or dyskinesia, represent a debilitating complication of levodopa therapy for Parkinson's disease. Although changes affecting D(1) and D(2) dopamine receptors have been studied in association with this condition, no causal relationship has yet been established. Taking advantage of a monkey brain bank constituted to study levodopa-induced dyskinesia, we report changes affecting D(1) and D(2) dopamine receptors within the striatum of normal, parkinsonian, nondyskinetic levodopa-treated parkinsonian, and dyskinetic levodopa-treated parkinsonian animals. Whereas D(1) receptor expression itself is not related to dyskinesia, D(1) sensitivity per D(1) receptor measured by D(1) agonist-induced [(35)S]GTPgammaS binding is linearly related to dyskinesia. Moreover, the striata of dyskinetic animals show higher levels of cyclin-dependent kinase 5 (Cdk5) and of the dopamine- and cAMP-regulated phosphoprotein of 32kDa (DARPP-32). Our data suggest that levodopa-induced dyskinesia results from increased dopamine D(1) receptor-mediated transmission at the level of the direct pathway.
非自主运动，即运动障碍，是帕金森病左旋多巴治疗的一种致残性并发症。尽管已经研究了影响D(1)和D(2)多巴胺受体的变化与这种情况的关系，但尚未建立因果关系。利用为研究左旋多巴诱发的运动障碍而建立的猴脑库，我们报告了正常、帕金森病、未发生运动障碍的左旋多巴治疗的帕金森病以及发生运动障碍的左旋多巴治疗的帕金森病动物纹状体内D(1)和D(2)多巴胺受体的变化。虽然D(1)受体表达本身与运动障碍无关，但通过D(1)激动剂诱导的[(35)S]GTPγS结合测量的每个D(1)受体的D(1)敏感性与运动障碍呈线性相关。此外，发生运动障碍的动物的纹状体显示出更高水平的细胞周期蛋白依赖性激酶5（Cdk5）和32 kDa的多巴胺和cAMP调节磷蛋白（DARPP-32）。我们的数据表明，左旋多巴诱发的运动障碍是由直接通路水平上多巴胺D(1)受体介导的传递增加所致。
