Strecker R E, Sharp T, Brundin P, Zetterström T, Ungerstedt U, Björklund A
Neuroscience. 1987 Jul;22(1):169-78. doi: 10.1016/0306-4522(87)90207-7.
The autoregulation of dopamine release and metabolism by intrastriatal grafts of mesencephalic dopamine neurons was examined in vivo using an intracerebral dialysis technique. Dopamine-rich cell suspension grafts were implanted into the head of the caudate putamen in rats with complete unilateral 6-hydroxydopamine lesion of the nigrostriatal dopamine pathway. Six months later behavioural tests indicated that the grafts had reversed the lesion-induced rotational behaviour. Extracellular levels of striatal dopamine and its metabolites 3,4-dihydroxyphenylacetic acid and homovanillic acid were monitored bilaterally in the halothane-anaesthetized grafted rat, both under basal conditions, and also following low (0.05 mg/kg) and high (0.5 mg/kg) doses of the dopamine receptor agonist apomorphine. The perfusate from the grafted striatum showed levels of dopamine which were not statistically different from those of the intact contralateral striatum, indicating that the baseline release of dopamine from the graft was close to normal. Similarly, 3-4-dihydroxyphenylacetic acid and homovanillic acid levels were well recovered on the grafted side (67% and 52%, respectively, of control values). Consistent with previous observations, levels of the serotonin metabolite 5-hydroxyindoleacetic acid measured in perfusate collected from the grafted side was elevated significantly above normal. Subsequent histological analysis revealed large grafts, rich in dopamine-containing neurons (mean +/- SEM number equalled 3138 +/- 630), giving rise to an approximately normal density of dopamine-containing fibres in the area of the host caudate putamen surrounding the probe. Treatment with 0.05 mg/kg (subcutaneous) apomorphine did not affect extracellular dopamine recovered from the grafted striatum, while extracellular DA decreased by a maximum of 30% on the intact side. However, a subsequent injection of 0.5 mg/kg apomorphine produced a large decrease of the dopamine recovered from both the grafted (maximum 40% decrease) and intact striata (maximum 80% decrease). Both the low and the high dose of apomorphine reduced extracellular dopamine metabolite levels, a response which was essentially similar for both the intact and grafted sides. Finally, the dopamine reuptake blocker nomifensine (10(-5) M) added to the perfusion medium produced similar large increases in dopamine in perfusates collected from both grafted and intact striata, while 3,4-dihydroxyphenylacetic acid and homovanillic acid did not change.(ABSTRACT TRUNCATED AT 400 WORDS)
利用脑内透析技术在体内研究了中脑多巴胺神经元纹状体内移植对多巴胺释放和代谢的自动调节作用。将富含多巴胺的细胞悬液移植到黑质纹状体多巴胺通路完全单侧6-羟基多巴胺损伤的大鼠尾状核头部。6个月后行为测试表明移植已逆转了损伤诱导的旋转行为。在氟烷麻醉的移植大鼠中，双侧监测纹状体多巴胺及其代谢物3,4-二羟基苯乙酸和高香草酸的细胞外水平，包括基础条件下以及给予低剂量（0.05mg/kg）和高剂量（0.5mg/kg）多巴胺受体激动剂阿扑吗啡之后。移植纹状体的灌流液显示多巴胺水平与完整对侧纹状体的水平无统计学差异，表明移植组织中多巴胺的基础释放接近正常。同样，移植侧3,4-二羟基苯乙酸和高香草酸水平也得到很好恢复（分别为对照值的67%和52%）。与先前观察结果一致，从移植侧收集的灌流液中测得的5-羟色胺代谢物5-羟基吲哚乙酸水平显著高于正常。随后的组织学分析显示移植组织较大，富含含多巴胺神经元（平均±标准误数量为3138±630），在围绕探针的宿主尾状核区域产生了近似正常密度的含多巴胺纤维。皮下注射0.05mg/kg阿扑吗啡对从移植纹状体回收的细胞外多巴胺无影响，而完整侧细胞外多巴胺最多降低30%。然而，随后注射0.5mg/kg阿扑吗啡使从移植（最大降低40%）和完整纹状体（最大降低80%）回收的多巴胺大幅减少。低剂量和高剂量阿扑吗啡均降低了细胞外多巴胺代谢物水平，完整侧和移植侧的反应基本相似。最后，向灌注培养基中添加多巴胺再摄取阻滞剂诺米芬辛（10⁻⁵M）使从移植和完整纹状体收集的灌流液中的多巴胺同样大幅增加，而3,4-二羟基苯乙酸和高香草酸未发生变化。（摘要截选至400字）
