May C H, Guilarte T R, Wagner H N, Vogel S
Department of Neurosurgery, Humboldt-University, Bereich Medizin (Charité), Berlin, Germany.
Neurodegeneration. 1994 Dec;3(4):305-13.
The present study examined the effect of chronic intrastriatal infusion of the dopamine receptor agonist lisuride on apomorphine-induced rotational behaviour and on D2-dopamine receptors in rats with unilateral 6-hydroxydopamine (6-OHDA) lesions of the nigrostriatal dopaminergic pathway. The completeness of the lesion of the right ascending nigrostriatal dopaminergic pathway was confirmed by apomorphine-induced rotation and [3H]-mazindol autoradiography. The intrastriatal infusion of lisuride (0.5 microgram/h) into the lesioned striatum for 2 weeks induced an immediate but temporary spontaneous contralateral rotation and a reduction of apomorphine-induced rotation of 47.2% relative to pre-lisuride infusion. The density of D2-receptors in the lisuride-infused striatum was significantly decreased by 40% relative to vehicle-infused 6-OHDA lesioned rats. The level of D2-dopamine receptors returned to normal levels 3 weeks after the termination of lisuride infusion. These results show that the intrastriatal infusion of lisuride reverses the behavioural and D2-dopamine receptor changes present in the 6-OHDA lesion rat model of Parkinson's disease.
本研究检测了向单侧黑质纹状体多巴胺能通路6-羟基多巴胺（6-OHDA）损伤大鼠的纹状体内长期输注多巴胺受体激动剂利苏瑞ide对阿扑吗啡诱导的旋转行为及D2-多巴胺受体的影响。通过阿扑吗啡诱导的旋转和[3H]-吗吲哚放射自显影术证实右侧黑质纹状体多巴胺能通路损伤的完整性。向损伤纹状体内输注利苏瑞ide（0.5微克/小时），持续2周，可立即引起短暂的对侧自发旋转，且与输注利苏瑞ide前相比，阿扑吗啡诱导的旋转减少了47.2%。与输注赋形剂的6-OHDA损伤大鼠相比，输注利苏瑞ide的纹状体内D2受体密度显著降低了40%。利苏瑞ide输注终止3周后，D2-多巴胺受体水平恢复至正常水平。这些结果表明，向纹状体内输注利苏瑞ide可逆转帕金森病6-OHDA损伤大鼠模型中存在的行为和D2-多巴胺受体变化。
