Carta Anna R, Frau Lucia, Pontis Silvia, Pinna Annalisa, Morelli Micaela
Department of Toxicology, University of Cagliari, via Ospedale 72, Cagliari, Italy.
Parkinsonism Relat Disord. 2008;14 Suppl 2:S165-8. doi: 10.1016/j.parkreldis.2008.04.023. Epub 2008 Jun 25.
Clinical evidence suggests that stimulation of the D(1) rather than D(2) dopamine receptor is related to the development of dyskinesias in Parkinson's disease (PD). We evaluated, in the 6-hydroxydopamine rat model of PD, sensitization of contralateral turning (SCT) behaviour and abnormal involuntary movements (AIMs) as behavioural parameters of dyskinetic response, and changes in zif-268 mRNA expression in striatonigral and striatopallidal neurons on subchronic administration of the D(2)/D(3) agonist ropinirole, defined as a mild dyskinetic drug in the clinic. Results were compared with previous findings on repeated L-dopa treatment. Ropinirole displayed a mild dyskinetic response characterized by SCT only, which contrasted with the presence of SCT in association with AIMs elicited by repeated L-dopa. Zif-268 mRNA levels were decreased in both striatonigral and striatopallidal neurons by ropinirole, in contrast to hyper-expression of zif-268 mRNA selectively induced by L-dopa in striatonigral neurons. Unbalanced responsiveness of striatal efferent neurons might represent a molecular correlate of high dyskinetic potential and AIMs in rats; in contrast, a balanced striatal output might underlie the low dyskinetic potential displayed by ropinirole.
临床证据表明，帕金森病（PD）中异动症的发生与多巴胺D(1)受体而非D(2)受体的刺激有关。在PD的6-羟基多巴胺大鼠模型中，我们评估了对侧旋转行为（SCT）的敏化和异常不自主运动（AIMs）作为异动症反应的行为参数，以及在亚慢性给予临床定义为轻度异动症药物的D(2)/D(3)激动剂罗匹尼罗后，黑质纹状体和纹状体苍白球神经元中zif-268 mRNA表达的变化。将结果与先前关于重复左旋多巴治疗的研究结果进行比较。罗匹尼罗表现出仅以SCT为特征的轻度异动症反应，这与重复左旋多巴引发的SCT与AIMs同时出现形成对比。与左旋多巴在黑质纹状体神经元中选择性诱导zif-268 mRNA的高表达相反，罗匹尼罗使黑质纹状体和纹状体苍白球神经元中的zif-268 mRNA水平均降低。纹状体传出神经元的反应性失衡可能是大鼠高异动症潜能和AIMs的分子关联；相反，平衡的纹状体输出可能是罗匹尼罗表现出低异动症潜能的基础。
