Jenkins T A, Chai S Y, Mendelsohn F A
Department of Medicine, University of Melbourne, Victoria, Australia.
Brain Res. 1997 Feb 14;748(1-2):137-42. doi: 10.1016/s0006-8993(96)01276-0.
The distribution of angiotensin II AT1 and AT2 receptor subtypes were mapped in the mouse brain by in vitro autoradiography. Along with a differing distribution of AT1 and AT2 receptors in the hind brain compared to the rat, moderate densities of AT1 receptors were observed in dopamine-rich regions, namely the caudate putamen and nucleus accumbens, previously observed in the human, but not rat or rabbit. Considering our previous anatomical and functional studies demonstrating an interaction between brain angiotensin II and dopaminergic systems, the effect of chronic treatment with the dopamine antagonist, haloperidol, on AT1 and AT2 receptor levels was investigated in the mouse brain. Haloperidol treatment for 21 days resulted in an increase in angiotensin II AT1 receptor levels in the nucleus accumbens, accompanied by an increase in dopamine D2 receptors, but no change in dopamine D1 receptors. Striatal AT1 receptors did not alter with treatment, nor did AT1 or AT2 receptors in a number of brain regions not associated with dopaminergic systems, such as the median preoptic nucleus, paraventricular hypothalamic nucleus, and nucleus of the solitary tract. The present study suggests that brain angiotensin II-dopamine interactions extend beyond the known effects on the nigrostriatal dopaminergic system, to the mesocorticolimbic dopaminergic system.
通过体外放射自显影法绘制了小鼠脑中血管紧张素 II AT1 和 AT2 受体亚型的分布图。与大鼠相比，小鼠后脑的 AT1 和 AT2 受体分布有所不同，在富含多巴胺的区域，即尾状壳核和伏隔核中观察到中等密度的 AT1 受体，此前在人类中观察到过，但在大鼠或兔子中未观察到。鉴于我们之前的解剖学和功能研究表明脑内血管紧张素 II 与多巴胺能系统之间存在相互作用，我们研究了多巴胺拮抗剂氟哌啶醇长期治疗对小鼠脑内 AT1 和 AT2 受体水平的影响。氟哌啶醇治疗 21 天导致伏隔核中血管紧张素 II AT1 受体水平升高，同时多巴胺 D2 受体增加，但多巴胺 D1 受体无变化。纹状体 AT1 受体在治疗后未改变，与多巴胺能系统无关的一些脑区，如视前正中核、下丘脑室旁核和孤束核中的 AT1 或 AT2 受体也未改变。本研究表明，脑内血管紧张素 II - 多巴胺相互作用不仅限于对黑质纹状体多巴胺能系统的已知影响，还扩展到了中脑皮质边缘多巴胺能系统。
