Yurek D M, Steece-Collier K, Collier T J, Sladek J R
Department of Neurobiology and Anatomy, University of Rochester School of Medicine and Dentistry, NY 14642.
Exp Brain Res. 1991;86(1):97-107. doi: 10.1007/BF00231044.
The effect of chronic levodopa treatment on the function of embryonic mesencephalic tissue grafts was assessed in rats by monitoring rotational behavior elicited by dopamine (DA) agonists before and after neural grafting. Rats were given unilateral 6-hydroxydopamine (6-OHDA) lesions of the nigrostriatal pathway and baseline measures of rotational behavior induced by D1 receptor stimulation, D2 receptor stimulation, or amphetamine were determined. Subsequently, DA grafts were implanted into the lesioned striatum and chronic regimens of either saline or levodopa began one day after neural grafting and were continued for 7 weeks. Rotational behavior elicited by the D1 agonist, SKF 38393, was completely attenuated throughout the six-week-period following the commencement of levodopa treatment, regardless of the absence or presence of a DA graft. Conversely, rotational behavior elicited by the D2 agonist, quinpirole, was significantly elevated in ungrafted animals receiving chronic levodopa. Grafted animals receiving chronic levodopa did not show a significant reduction in rotational behavior, whereas grafted animals receiving chronic saline showed a significant 67% reduction in quinpirole-induced rotational behavior. Amphetamine-induced rotational behavior was reduced in both levodopa and saline treated grafted animals, however grafted animals receiving chronic levodopa treatment showed a reduction of rotational behavior that was uncharacteristic and less compensatory than that observed in grafted animals receiving chronic saline treatment. Morphology of grafts indicate that there were areas of impaired neurite outgrowth of TH-positive fibers in animals treated with levodopa. The results of the present study suggest that the impaired recovery in quinpirole- and amphetamine-induced rotational behavior in grafted animals receiving chronic levodopa treatment may be related to (1) impaired graft function, (2) an alteration in pre- and postsynaptic mechanisms in the host DAergic system, or (3) a combined effect of (1) and (2).
通过监测神经移植前后多巴胺（DA）激动剂引发的旋转行为，评估了慢性左旋多巴治疗对大鼠胚胎中脑组织移植功能的影响。给大鼠单侧黑质纹状体通路注射6-羟基多巴胺（6-OHDA）损伤，并测定D1受体刺激、D2受体刺激或苯丙胺诱导的旋转行为的基线指标。随后，将DA移植物植入受损纹状体，神经移植后一天开始给予生理盐水或左旋多巴的慢性给药方案，并持续7周。无论是否存在DA移植物，在左旋多巴治疗开始后的六周内，D1激动剂SKF 38393引发的旋转行为完全减弱。相反，在接受慢性左旋多巴治疗的未移植动物中，D2激动剂喹吡罗引发的旋转行为显著升高。接受慢性左旋多巴治疗的移植动物的旋转行为没有显著降低，而接受慢性生理盐水治疗的移植动物的喹吡罗诱导的旋转行为显著降低了67%。左旋多巴和生理盐水处理的移植动物中，苯丙胺诱导的旋转行为均降低，然而，接受慢性左旋多巴治疗的移植动物的旋转行为降低不典型，且补偿性低于接受慢性生理盐水治疗的移植动物。移植物形态学表明，接受左旋多巴治疗的动物中，TH阳性纤维的神经突生长存在受损区域。本研究结果表明，接受慢性左旋多巴治疗的移植动物中，喹吡罗和苯丙胺诱导的旋转行为恢复受损可能与以下因素有关：（1）移植物功能受损；（2）宿主多巴胺能系统突触前和突触后机制的改变；或（3）（1）和（2）的联合作用。
