Effects of L-Dopa and pramipexole on plasticity induced by QPS in human motor cortex
Effects of L-Dopa and pramipexole on plasticity induced by QPS in human motor cortex
复制标题
DOI：
10.1007/s00702-015-1374-8
复制
发表时间：
2015-09-01
影响因子：
3.3
通讯作者：
Ugawa, Yoshikazu
中科院分区：
文献类型：
--
作者：
Enomoto, Hiroyuki;Terao, Yasuo;Ugawa, Yoshikazu
帕金森病（PD）患者的大脑，特别是纹状体，存在异常的可塑性。虽然左旋多巴和多巴胺激动剂仍然是PD治疗的主要手段，但它们对皮质可塑性的不同影响尚不清楚。我们应用四脉冲刺激（QPS）在10名正常人的初级运动皮层（M1）诱导双向长期运动皮层可塑性。高频QPS5（脉冲间隔为5ms）在初级运动皮层（M1）中诱导出长时程增强（LTP）样效应，而低频QPS50（脉冲间隔为50ms）诱导出长时程抑制（LTD）样效应，刺激脉冲停止后这种效应持续90min。在双盲随机安慰剂对照交叉设计中，在应用QPS前30分钟给予受试者左旋多巴卡比多巴100 mg、普拉克索1.5 mg [150 mg LED（左旋多巴等效剂量）]或安慰剂。与安慰剂相比，左旋多巴增强了LTP和LTD样可塑性。相反，普拉克索既不调节LTP样效应，也不调节LTD样效应。缺乏普拉克索对LTP的增强作用与D1激活增强LTP的发现一致，因为普拉克索几乎是一种纯粹的D2激动剂。普拉克索对LTD增强作用的缺乏也与LTD需要D1和D2共激活的发现一致。这是第一份报告表明多巴胺增强了人脑中的LTD和LTP，并且D1和D2的共激活是正常人LTD增强的必要条件。
Abnormal plasticity has been reported in the brain of patients with Parkinson's disease (PD), especially in the striatum. Although both l-Dopa and dopamine agonist remain to be the mainstay of the treatment in PD, their differential effects on cortical plasticity are unclear. We applied quadripulse stimulation (QPS) over the primary motor cortex (M1) in ten normal subjects to induce bidirectional long-term motor cortical plasticity. A long-term potentiation (LTP)-like effect was induced in the primary motor cortex (M1) by high-frequency QPS5 (interpulse interval of 5 ms) over M1, whereas a long-term depression (LTD)-like effect was induced by low-frequency QPS50 (interpulse interval of 50 ms), and the effects lasted up to 90 min after the stimulation pulses have ceased. In a double-blind randomized placebo-controlled crossover design, l-Dopa carbidopa 100 mg, pramipexole 1.5 mg [150 mg LED (l-Dopa equivalent dose)], or placebo was administered to the subjects 30 min before applying QPS. l-Dopa enhanced both LTP- and LTD-like plasticity as compared to placebo. In contrast, neither an LTP-like effect nor an LTD-like effect was modulated by pramipexole. The lack of LTP enhancement by pramipexole is compatible with the finding that D1 activation strengthens LTP because pramipexole is almost purely a D2 agonist. The lack of LTD enhancement by pramipexole is also consistent with the finding that both D1 and D2 coactivation is required for LTD. This is the first report to show that dopamine enhances LTD as well as LTP in the human brain and that coactivation of D1 and D2 is a requisite for LTD enhancement in normal humans.