Department of Neurology, Washington University School of Medicine, Saint Louis, Missouri, USA.
Mov Disord. 2013 Dec;28(14):2002-6. doi: 10.1002/mds.25720. Epub 2013 Oct 21.
Multiple studies have demonstrated decreases in striatal D2-like (D2, D3) radioligand binding in primary focal dystonias. Although most investigations have focused on D2-specific receptors (D2R), a recent study suggests that the decreased D2-like binding may be due to a D3-specific (D3R) abnormality. However, only limited data exist on the role of D1-specific receptors (D1R) and the D1R-mediated pathways within basal ganglia in dystonia. Metabolic positron emission tomography (PET) data in primary generalized dystonia suggest resting state over activity in the D1R-mediated direct pathway, leading to excessive disinhibition of motor cortical areas. This work investigated whether striatal D1-like receptors are affected in primary focal dystonias.
Striatal-specific (caudate and putamen) binding of the D1-like radioligand [(11)C]NNC 112 was measured using PET in 19 patients with primary focal dystonia (cranial, cervical, or arm) and 18 controls.
No statistically significant difference was detected in striatal D1-like binding between the two groups. The study had 91% power to detect a 20% difference, indicating that false-negative results were unlikely.
Because [(11)C]NNC 112 has high affinity for D1-like receptors, very low affinity for D2-like receptors, and minimal sensitivity to endogenous dopamine levels, we conclude that D1-like receptor binding is not impaired in these primary focal dystonias.
多项研究表明,原发性局灶性肌张力障碍患者纹状体中 D2 样(D2、D3)放射性配体结合减少。尽管大多数研究都集中在 D2 特异性受体(D2R)上,但最近的一项研究表明,减少的 D2 样结合可能是由于 D3 特异性(D3R)异常。然而,关于 D1 特异性受体(D1R)和基底神经节中 D1R 介导的途径在肌张力障碍中的作用,仅有有限的数据。原发性全身性肌张力障碍的代谢正电子发射断层扫描(PET)数据表明,D1R 介导的直接途径中存在静息状态过度活动,导致运动皮质区域过度抑制。这项工作研究了原发性局灶性肌张力障碍中纹状体 D1 样受体是否受到影响。
使用 PET 测量 19 例原发性局灶性肌张力障碍(颅、颈或臂)患者和 18 例对照者纹状体特异性(尾状核和壳核)D1 样放射性配体[11C]NNC 112 的结合。
两组间纹状体 D1 样结合无统计学差异。该研究有 91%的效能检测到 20%的差异,表明假阴性结果不太可能。
由于[11C]NNC 112 对 D1 样受体具有高亲和力,对 D2 样受体具有低亲和力,对内源性多巴胺水平的敏感性最小,我们得出结论,这些原发性局灶性肌张力障碍中 D1 样受体结合没有受损。