ORGANIZATION OF DOPAMINE D1 AND D2 RECEPTORS IN HUMAN STRIATUM - RECEPTOR AUTORADIOGRAPHIC STUDIES IN HUNTINGTONS-DISEASE AND SCHIZOPHRENIA
ORGANIZATION OF DOPAMINE D1 AND D2 RECEPTORS IN HUMAN STRIATUM - RECEPTOR AUTORADIOGRAPHIC STUDIES IN HUNTINGTONS-DISEASE AND SCHIZOPHRENIA
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DOI：
10.1002/syn.890020511
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发表时间：
1988-01-01
期刊：
影响因子：
2.3
通讯作者：
WINOKUR, A
中科院分区：
文献类型：
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作者：
JOYCE, JN;LEXOW, N;WINOKUR, A
定量放射自显影技术用于检查亨廷顿病 (HD) 和精神分裂症对纹状体多巴胺 (DA) D1 和 D2 受体组织的影响。尽管 HD 病例的纹状体显示 D1 ([3H]SCH 23390) 和 D2 ([3H]spiroperidol) 受体密度降低，但 D2 受体丢失的模式与 D1 受体丢失的模式并不匹配。 HD 中 DA D1 受体的损失 (65%) 远远大于 D2 受体的损失 (28%)。虽然对两种受体亚型的影响存在背腹梯度，但 HD 对腹侧壳核 (PUT) 和伏隔核 (NAS) 中的 D2 受体的影响很小。同样，毒蕈碱 M1 和 M2 受体在 HD 中表现出不同的改变模式。用[3H]N-甲基东莨菪碱标记的M2亚型（在存在过量哌仑西平以封闭M1位点的情况下），比用[3H]哌仑西平标记的M1受体亚型消耗得更多。尽管HD对DA末端[3H]马吲哚标记的影响更加异质，但HD病例纹状体的传入输入似乎相对保留。在精神分裂症病例中，我们的放射自显影研究证实了先前的报告，即许多精神分裂症患者纹状体中 D2 受体密度升高。尽管已知这三个病例中的两个没有接受过神经麻痹剂治疗，但这种增加是显而易见的，而第三个病例也可能是药物本身。然而，NAS（164％）和腹侧PUT（173％）的增加远远大于纹状体背侧（68％）。精神分裂症患者纹状体中[3H]马吲哚标记的D1受体和DA末端密度与对照病例无显着差异。因此，在 HD 和精神分裂症中，D2/D1 受体的比例发生了有利于 D2 群体的变化，特别是在 NAS 中。
The technique of quantitative autoradiography was used to examined the effects of Huntington''s disease (HD) and schizophrenia on the organization of striatal dopamine (DA) D1 and D2 receptors. Whereas the striatum of HD cases showed a reduction in the density of D1 ([3H]SCH 23390) and D2 ([3H]spiroperidol) receptors, the patterning of D2 receptor loss did not match that of the D1 receptor loss. The HD loss of DA D1 receptors (65%) is far greater than the loss of D2 receptors (28%). Whereas there was a dorsal-ventral gradient of effect on both receptor subtypes, the effects of HD on D2 receptors in the ventral putamen (PUT) and nucleus accumben septi (NAS) were minimal. Similarly, muscarinic M1 and M2 receptors demonstrate different patterns of alteration in HD. The M2 subtype, labeled with [3H]N-methylscopolamine (in the present of excess pirenzepine to occlude M1 sites), was depleted far more than the M1 receptor subtype, labeled with [3H]pirenzepine. Although the effects of HD on [3H]mazindol labeling of DA terminals were more heterogeneous, there appeared to be a relative preservation of this afferent input to the striatum of the HD cases. In the schizophrenic cases, our autoradiographic studies confirm previous reports of an elevation of D2 receptor density in the striata of many schizophrenics. This increase was evident even though two of the three cases were known to have not been treated with neuropletics, and the third case may also have been drug native. However, the increase was far greater in the NAS (164%) and ventral PUT (173%) than more dorsally in the striatum (68%). The density of D1 receptors and DA terminals labeled with [3H]mazindol in the striatum of schizophrenics was not significantly different from that of control cases. Thus in both HD and schizophrenia, the ratio of D2/D1 receptors is altered in favor of the D2 population, particularly in the NAS.