Yu J, Coirini H, Källström L, Wiesel F A, Johnson A E
Department of Psychiatry, Ulleråker, University Hospital, Uppsala University, Sweden.
Synapse. 1998 Sep;30(1):38-48. doi: 10.1002/(SICI)1098-2396(199809)30:1<38::AID-SYN5>3.0.CO;2-L.
Dopamine D1-receptor binding in the basal ganglia is differentially regulated by subtype nonspecific dopamine antagonists such as the antipsychotic, Fluphenazine. The purpose of the present study was to determine the relative contributions of D1 and D2 receptor systems in the regulation of basal ganglia D1-receptor binding. Rats were injected twice daily for 21 days with saline, the D1-receptor antagonist, SCH-23390, the D2-receptor antagonist, Raclopride, or both SCH-23390 and Raclopride. Dopamine D1-receptor levels (as indicated by [125I]SCH-23982 binding) and mRNA expression were measured using receptor autoradiographic and in situ hybridization histochemical techniques. [125I]NCQ-298 binding to D2-receptors was also measured as a positive control for the effects of Raclopride. SCH-23390 administration independently increased [125I]SCH-23982 binding in a region-dependent manner with the greatest increases occurring in the entopeduncular nucleus. SCH-23390 also increased D1-receptor mRNA expression in specific striatal subregions suggesting that increases in binding were related to changes in receptor synthesis. In addition, Raclopride independently enhanced D2 binding with comparable increases observed in extrastriatal regions and increases of a lesser magnitude in the striatum. These data show that the modulation of basal ganglia D1-receptor binding observed in animals treated with nonselective antagonists is due primarily to the blockade of D1-receptors. The differential enhancement in basal ganglia D1 binding observed after D1-receptor blockade may be due to anatomical or phenotypic heterogeneity within the population of striatal D1-receptor synthesizing neurons. Similarly, the differential enhancement in striatal and extrastriatal D2-receptor binding may be due to differences in the regulation of striatal and extrastriatal D2-receptor synthesizing neurons.
基底神经节中的多巴胺 D1 受体结合受到非亚型特异性多巴胺拮抗剂（如抗精神病药物氟奋乃静）的不同调节。本研究的目的是确定 D1 和 D2 受体系统在调节基底神经节 D1 受体结合中的相对作用。大鼠每天注射两次，持续 21 天，分别注射生理盐水、D1 受体拮抗剂 SCH-23390、D2 受体拮抗剂雷氯必利，或同时注射 SCH-23390 和雷氯必利。使用受体放射自显影和原位杂交组织化学技术测量多巴胺 D1 受体水平（以 [125I]SCH-23982 结合表示）和 mRNA 表达。还测量了 [125I]NCQ-298 与 D2 受体的结合，作为雷氯必利作用的阳性对照。给予 SCH-23390 以区域依赖性方式独立增加 [125I]SCH-23982 结合，在内侧缰核中增加最为显著。SCH-23390 还增加了特定纹状体亚区域中 D1 受体 mRNA 的表达，表明结合的增加与受体合成的变化有关。此外，雷氯必利独立增强 D2 结合，在纹状体以外区域观察到类似的增加，在纹状体中增加幅度较小。这些数据表明，在用非选择性拮抗剂治疗的动物中观察到的基底神经节 D1 受体结合的调节主要是由于 D1 受体的阻断。D1 受体阻断后基底神经节 D1 结合的差异增强可能是由于纹状体 D1 受体合成神经元群体中的解剖学或表型异质性。同样，纹状体和纹状体以外区域 D2 受体结合的差异增强可能是由于纹状体和纹状体以外区域 D2 受体合成神经元调节的差异。
