Berger K, Przedborski S, Cadet J L
Department of Neurology, Columbia University, New York, NY 10032.
Brain Res Bull. 1991 Feb;26(2):301-7. doi: 10.1016/0361-9230(91)90242-c.
Quantitative receptor autoradiography was used to assess the effects of unilateral intrastriatal injections of 6-hydroxydopamine (6-OHDA) on the distribution of D1 and D2 dopamine (DA) receptors and of DA uptake sites in the mesostriatal pathway. [3H]Mazindol-labeled DA uptake sites were reduced both in the striatum (-97%) and in the substantia nigra pars compacta (SNpc) (-88%) on the injected side. There were also significant decreases of dopamine uptake sites in the nucleus accumbens (NAc) (-73%) and in the ventral tegmental area (VTA) (-70%). Changes in [3H]mazindol binding were also found within the contralateral VTA (-30%) and SNpc (-13%) but not in the contralateral-striatum. [3H]SCH23390-labeled D1 receptors were significantly reduced in the dorsomedial (-18%) and ventromedial (-14%) aspects of the striatum ipsilateral to the side of the lesions. In contrast, the concentration of [3H]spiperone-labeled D2 receptors was not altered. There were also significant decreases in D1 (-18%) and of D2 (-27%) receptors in the SNpc and of D1 (-10%) in the SN pars reticulata (SNpr). These results suggest that oxyradical-induced damage in striatal DA terminals could lead to retrograde changes in the SNpc. In addition, the data indicate that unilateral striatal damage can result in bilateral changes in the SNpc, thus confirming the interdependence of the two nigrostriatal pathways in rats.
采用定量受体放射自显影术评估单侧纹状体内注射6-羟基多巴胺（6-OHDA）对中脑纹状体通路中D1和D2多巴胺（DA）受体分布以及DA摄取位点的影响。注射侧纹状体（-97%）和黑质致密部（SNpc，-88%）中[3H]马吲哚标记的DA摄取位点减少。伏隔核（NAc，-73%）和腹侧被盖区（VTA，-70%）中的多巴胺摄取位点也显著减少。在对侧VTA（-30%）和SNpc（-13%）中也发现了[3H]马吲哚结合的变化，但对侧纹状体中未发现。[3H]SCH23390标记的D1受体在损伤侧同侧纹状体的背内侧（-18%）和腹内侧（-14%）显著减少。相比之下，[3H]螺哌隆标记的D2受体浓度未改变。SNpc中的D1（-18%）和D2（-27%）受体以及黑质网状部（SNpr）中的D1（-10%）也显著减少。这些结果表明，纹状体DA终末的氧自由基诱导损伤可能导致SNpc的逆行性变化。此外，数据表明单侧纹状体损伤可导致SNpc的双侧变化，从而证实了大鼠两条黑质纹状体通路的相互依赖性。
