Zetterström T, Herrera-Marschitz M, Ungerstedt U
Brain Res. 1986 Jun 18;376(1):1-7. doi: 10.1016/0006-8993(86)90893-0.
Amphetamine- and L-DOPA-induced changes in extracellular levels of striatal dopamine (DA) were monitored during rotational behaviour in rats with a unilateral 6-hydroxydopamine (6-OHDA) lesion of the nigrostriatal DA pathway. In vivo DA release measurements were obtained using intracerebral dialysis combined with high-performance liquid chromatography with electrochemical detection (HPLC-ED). In unilaterally denervated rats no DA was detected in dialysates collected from the striatum ipsilateral to the lesion while the contralateral side showed a compensatory increase in basal DA levels when compared to non-lesioned controls. Amphetamine (0.5-5.0 mg/kg s.c.) caused a dose-dependent release of DA in the striatum of normal rats and in the intact striatum of DA denervated rats but did not significantly release DA in the lesioned striatum. In response to amphetamine (0.5-5.0 mg/kg s.c.) lesioned animals showed dose-related ipsilateral rotational behaviour which in general correlated well with the time-course change in, and the total amount of, DA release in striatum contralateral to the lesion. In contrast to amphetamine, in lesioned rats, the DA precursor L-DOPA (20 mg/kg s.c.) induced readily detectable amounts of DA in dialysates collected from the DA denervated striatum. The L-DOPA-induced appearance of DA, which approached basal DA levels seen on the intact side, was concomitant with contralateral rotational behaviour. However, the time-course change in DA levels did not closely correlate with the apparently two-peak pattern of contralateral rotation induced by L-DOPA.
在黑质纹状体多巴胺(DA)通路单侧6-羟基多巴胺(6-OHDA)损伤的大鼠旋转行为过程中,监测了苯丙胺和左旋多巴(L-DOPA)诱导的纹状体细胞外DA水平变化。使用脑内透析结合高效液相色谱-电化学检测(HPLC-ED)进行体内DA释放测量。在单侧去神经支配的大鼠中,从损伤同侧纹状体收集的透析液中未检测到DA,而与未损伤的对照相比,对侧基底DA水平出现代偿性升高。苯丙胺(0.5-5.0mg/kg皮下注射)可使正常大鼠纹状体以及DA去神经支配大鼠完整纹状体中的DA呈剂量依赖性释放,但在损伤纹状体中未显著释放DA。对苯丙胺(0.5-5mg/kg皮下注射)有反应的损伤动物表现出与剂量相关的同侧旋转行为,这通常与损伤对侧纹状体中DA释放的时程变化和总量密切相关。与苯丙胺不同,在损伤大鼠中,DA前体L-DOPA(20mg/kg皮下注射)在从DA去神经支配的纹状体收集的透析液中诱导出易于检测到的DA量。L-DOPA诱导的DA出现接近完整侧所见的基础DA水平,同时伴有对侧旋转行为。然而,DA水平的时程变化与L-DOPA诱导的对侧旋转的明显双峰模式并不密切相关。