Trugman J M, Wooten G F
Brain Res. 1986 Aug 6;379(2):264-74. doi: 10.1016/0006-8993(86)90780-8.
Using [14C]2-deoxyglucose autoradiography, we have studied the effects of systemically administered L-DOPA (10, 25 and 50 mg/kg s.c.) on regional cerebral glucose utilization (RCGU) in rats with unilateral substantia nigra lesions. In comparison with lesioned rats treated with saline, the lesioned-DOPA treated rats demonstrated contralateral turning and RCGU changes in both ipsilateral and contralateral brain regions. L-DOPA treatment markedly increased RCGU in the ipsilateral entopeduncular nucleus (EP) and substantia nigra pars reticulata (SNr), cell groups that receive direct striatal input and function as major outflow pathways of corpus striatal activity. In contrast, L-DOPA did not alter RCGU in the globus pallidus (GP), supporting the thesis that dopamine (DA) has different effects on striatal outflow to the GP compared with outflow to both the EP and SNr. Moderate RCGU increases were observed in the ipsilateral subthalamic nucleus (STN), lateral midbrain reticular formation (LMRF), and deep layers of the superior colliculus (DLSC), all regions which receive direct projections from the GP, EP or SNr. L-DOPA decreased RCGU in the ipsilateral lateral habenular nucleus (LHN) and increased RCGU in the contralateral LHN, changes that we suggest are mediated via altered neuronal activity in the striatum and EP. The results suggest that systemically administered L-DOPA, after conversion to DA in the brain, interacts with supersensitive DA receptors in the DA-depleted striatum to selectively activate efferent pathways. Furthermore, the data suggest that the LMRF and DLSC are functionally activated during L-DOPA induced turning and support the hypothesis that nigroreticular and nigrocollicular projections are of physiologic significance in the expression of striatal activity.
利用[14C]2-脱氧葡萄糖放射自显影技术，我们研究了全身给予左旋多巴（10、25和50mg/kg皮下注射）对单侧黑质损伤大鼠局部脑葡萄糖利用（RCGU）的影响。与用生理盐水处理的损伤大鼠相比，用左旋多巴处理的损伤大鼠表现出对侧旋转以及同侧和对侧脑区的RCGU变化。左旋多巴治疗显著增加了同侧内苍白球核（EP）和黑质网状部（SNr）的RCGU，这两个细胞群接受来自纹状体的直接输入，并作为纹状体活动的主要传出通路发挥作用。相比之下，左旋多巴并未改变苍白球（GP）的RCGU，支持了多巴胺（DA）对纹状体向GP的传出与向EP和SNr的传出具有不同作用的论点。在同侧丘脑底核（STN）、外侧中脑网状结构（LMRF）和上丘深层（DLSC）观察到中度的RCGU增加，所有这些区域都接受来自GP、EP或SNr的直接投射。左旋多巴降低了同侧外侧缰核（LHN）的RCGU，并增加了对侧LHN的RCGU，我们认为这些变化是通过纹状体和EP中神经元活动的改变介导的。结果表明，全身给予的左旋多巴在脑内转化为DA后，与DA耗竭的纹状体中超敏的DA受体相互作用，选择性地激活传出通路。此外，数据表明，在左旋多巴诱导的旋转过程中，LMRF和DLSC在功能上被激活，并支持黑质网状和黑质上丘投射在纹状体活动表达中具有生理意义的假说。
