Levodopa (L-DOPA) is the classical gold standard treatment for Parkinson's disease. However, its chronic administration can lead to the development of L-DOPA-induced dyskinesias (LIDs). Dysregulation of the nitric oxide–cyclic guanosine monophosphate pathway in striatal networks has been linked to deficits in corticostriatal transmission in LIDs. This study investigated the effects of the nitric oxide (NO) donor sodium nitroprusside (SNP) on behavioural and electrophysiological outcomes in sham-operated and 6-hydroxydopamine-lesioned rats chronically treated with vehicle or L-DOPA, respectively. In sham-operated animals, systemic administration of SNP increased the spike probability of putative striatal medium spiny neurons (MSNs) in response to electrical stimulation of the primary motor cortex. In 6-hydroxydopamine-lesioned animals, SNP improved the stepping test performance without exacerbating abnormal involuntary movements. Additionally, SNP significantly increased the responsiveness of putative striatal MSNs in the dyskinetic striatum. These findings highlight the critical role of the NO signalling pathway in facilitating the responsiveness of striatal MSNs in both the intact and dyskinetic striata. The study suggests that SNP has the potential to enhance L-DOPA's effects in the stepping test without exacerbating abnormal involuntary movements, thereby offering new possibilities for optimizing Parkinson's disease therapy. In conclusion, this study highlights the involvement of the NO signalling pathway in the pathophysiology of LIDs.

中文翻译：

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硝普钠可增强左旋多巴诱导的运动障碍大鼠模型的迈步测试性能并增加中型棘神经元对皮质输入的反应性

左旋多巴（L-DOPA）是治疗帕金森病的经典金标准。然而，长期服用可能会导致左旋多巴引起的运动障碍（LID）的发生。纹状体网络中一氧化氮-环磷酸鸟苷途径的失调与 LID 中皮质纹状体传输的缺陷有关。本研究调查了一氧化氮 (NO) 供体硝普钠 (SNP) 对分别长期接受媒介物或左旋多巴治疗的假手术大鼠和 6-羟基多巴胺损伤大鼠的行为和电生理结果的影响。在假手术动物中，全身施用 SNP 增加了假定的纹状体中型多棘神经元 (MSN) 对初级运动皮层电刺激的反应的尖峰概率。在 6-羟基多巴胺损伤的动物中，SNP 改善了迈步测试表现，而不会加剧异常的不随意运动。此外，SNP 显着增加了运动障碍纹状体中假定的纹状体 MSN 的反应性。这些发现强调了 NO 信号通路在促进完整纹状体和运动障碍纹状体中纹状体 MSN 反应性中的关键作用。该研究表明，SNP有潜力增强L-DOPA在迈步测试中的效果，而不加剧异常的不随意运动，从而为优化帕金森病治疗提供新的可能性。总之，本研究强调了 NO 信号通路在 LID 病理生理学中的参与。