Touchet N, Bennett J P
Department of Neurology, University of Virginia School of Medicine, Charlottesville 22908.
Neuropharmacology. 1989 Nov;28(11):1217-22. doi: 10.1016/0028-3908(89)90214-1.
Idiopathic Parkinson's Disease arises from the progressive loss of dopamine (DA)-utilizing neurons of the nigrostriatum and responds to the replacement of DA with L-dihydroxyphenylalanine (L-DOPA). In awake rats, with unilateral lesions induced with 6-hydroxydopamine (6-OHDA) of the DA-utilizing nigrostriatal pathway, treatment with L-DOPA causes the rapid onset of brisk contralateral turning behaviour. In urethane-anesthetized rats with identical unilateral lesions of the nigrostriatum, dialysis of the striatum, performed before and after the systemic administration of L-DOPA (25 mg/kg i.p.), did not demonstrate any alteration in extracellular DA in the striatum which was DA-deprived compared to intact striata. After treatment with L-DOPA extracellular levels of the metabolites of DA. DOPAC and HVA increased several fold. These results suggest: (a) DA neurons surviving after extensive lesions with 6-OHDA can compensate for loss of DA in the striatum and maintain extracellular fluid (and presumably synaptic) concentrations of DA; (b) in striata with extensive depletion of DA L-DOPA undergoes rapid decarboxylation to DA, followed by catabolism to DOPAC and HVA; and (c) in urethane-anesthetized animals, DA formed from DOPA does not appear to enter a releasable pool.
特发性帕金森病源于黑质纹状体中利用多巴胺（DA）的神经元的渐进性丧失，并对用左旋多巴（L-DOPA）替代DA有反应。在清醒大鼠中，用6-羟基多巴胺（6-OHDA）诱导黑质纹状体利用DA的通路单侧损伤后，给予L-DOPA治疗会导致对侧快速出现轻快的旋转行为。在具有相同单侧黑质纹状体损伤的乌拉坦麻醉大鼠中，在全身给予L-DOPA（25mg/kg腹腔注射）前后对纹状体进行透析，与完整纹状体相比，在DA缺乏的纹状体中未显示细胞外DA有任何变化。用L-DOPA治疗后，DA的代谢产物二羟基苯乙酸（DOPAC）和高香草酸（HVA）的细胞外水平增加了几倍。这些结果表明：（a）用6-OHDA广泛损伤后存活的DA神经元可以补偿纹状体中DA的损失，并维持细胞外液（可能还有突触）中DA的浓度；（b）在DA大量耗竭的纹状体中，L-DOPA迅速脱羧形成DA，随后分解代谢为DOPAC和HVA；（c）在乌拉坦麻醉的动物中，由多巴形成的DA似乎不会进入可释放池。
