Levodopa-Induced Dyskinesia Is Strongly Associated with Resonant Cortical Oscillations
Levodopa-Induced Dyskinesia Is Strongly Associated with Resonant Cortical Oscillations
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DOI：
10.1523/jneurosci.3047-12.2012
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发表时间：
2012-11-21
影响因子：
5.3
通讯作者：
Petersson, Per
中科院分区：
文献类型：
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作者：
Halje, Par;Tamte, Martin;Petersson, Per
遗憾的是，使用多巴胺前体左旋多巴治疗帕金森氏症的标准药物治疗受到逐渐发展的致残性不自主运动的限制，其潜在原因尚不清楚。本研究表明，左旋多巴诱导的半帕金森大鼠运动障碍与左旋多巴治疗后初级运动皮层明显的80 Hz局部场电位振荡密切相关。当在皮质表面应用多巴胺拮抗剂阻断这种振荡时，运动障碍症状消失。异常的皮质振荡是一个关键的病理生理机制，这一发现要求对当前流行的假设进行修正，该假设将左旋多巴诱导的运动障碍与纹状体对多巴胺的敏感性改变联系起来。除了对帕金森病的治疗具有重要意义外，发现的病理生理机制也可能在涉及皮质功能障碍的其他几种精神和神经疾病中发挥作用。
The standard pharmacological treatment for Parkinson's disease using the dopamine precursor levodopa is unfortunately limited by gradual development of disabling involuntary movements for which the underlying causes are poorly understood. Here we show that levodopa-induced dyskinesia in hemiparkinsonian rats is strongly associated with pronounced 80 Hz local field potential oscillations in the primary motor cortex following levodopa treatment. When this oscillation is interrupted by application of a dopamine antagonist onto the cortical surface the dyskinetic symptoms disappear. The finding that abnormal cortical oscillations are a key pathophysiological mechanism calls for a revision of the prevailing hypothesis that links levodopa-induced dyskinesia to an altered sensitivity to dopamine only in the striatum. Apart from having important implications for the treatment of Parkinson's disease, the discovered pathophysiological mechanism may also play a role in several other psychiatric and neurological conditions involving cortical dysfunction.