Long-term changes of striatal dopamine D-2 receptors in patients with Parkinson's disease: A study with positron emission tomography and [C-11]Raclopride
Long-term changes of striatal dopamine D-2 receptors in patients with Parkinson's disease: A study with positron emission tomography and [C-11]Raclopride
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DOI：
10.1002/mds.870120107
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发表时间：
1997-01-01
影响因子：
8.6
通讯作者：
Leenders, KL
中科院分区：
文献类型：
--
作者：
Antonini, A;Schwarz, J;Leenders, KL
我们使用[C-11]雷氯必利（RACLO）和正电子发射断层扫描（PET）研究了9例帕金森病（PD）患者在早期药物初治阶段和3-5年后的纵向纹状体多巴胺D-2受体结合，其中7例出现运动波动。患者接受左旋多巴和多巴胺激动剂联合治疗。将数据与10名相同年龄范围的健康对照进行比较。最初，与对照组相比，PD患者显示壳核中RACLO摄取显著增加（p < 0.04）。尾状核显示值在正常范围内。3-5年后，与基线相比，壳核（p < 0.03）和尾状核（p < 0.03）中的RACLO结合率显著降低。壳核中的值现在处于对照范围内，尾状核中的值降低（p < 0.05）。与第一次PET扫描相比，“关闭"时的临床评分显著恶化（p < 0.0005）。本文报告的9例PD患者在治疗开始后3-4个月进行了研究，当时未显示最初增加的RACLO结合能力降低（先前发表的数据）。这些结果表明，长期下调纹状体多巴胺D-2受体结合在PD。PD患者纹状体中的受体变化可能由慢性多巴胺能治疗诱导，或独立于治疗发生，这是突触后多巴胺能系统对黑质纹状体神经元进行性衰退的结构适应的结果。
We used [C-11]raclopride (RACLO) and positron emission tomography (PET) to study longitudinally striatal dopamine D-2 receptor binding in nine patients with Parkinson's disease (PD) at an early drug-naive stage and 3-5 years later, when motor fluctuations had appeared in seven of them. Patients were treated with a combination of levodopa and dopamine agonists. Data were compared with 10 healthy controls in the same age range. Initially, patients with PD showed a significant increase of RACLO uptake in the putamen compared with controls (p < 0.04). The caudate nucleus revealed values in the normal range. Alter 3-5 years, RACLO binding was significantly reduced in the putamen (p < 0.03) and caudate nucleus (p < 0.03) compared with baseline. Values were now in the control range in the putamen and reduced in the caudate nucleus (p < 0.05). The clinical score at ''off'' had significantly worsened (p < 0.0005) compared with the first PET scan. The nine PD patients reported here had already been investigated 3-4 months after therapy began and at that time did not show a reduction of the initially increased RACLO binding capacity (data published previously). These results indicate long-term downregulation of striatal dopamine D-2 receptor binding in PD. Receptor changes in the striatum of patients with PD may be induced by chronic dopaminergic therapy or occur independently of treatment, as a result of structural adaptation of the postsynaptic dopaminergic system to the progressive decline of nigrostriatal neurons.