Mura A, Feldon J, Mintz M
Behavioral Biology Laboratory, Institute of Toxicology, ETH, Schorenstrasse 16, CH-8603 Schwerzenbach, Switzerland.
Brain Res. 1998 Oct 12;808(1):48-55. doi: 10.1016/s0006-8993(98)00791-4.
A traditional view holds the belief that the behavioral effects of l-dihydroxyphenilalanine (l-DOPA) in Parkinsonian patients are achieved through the action of the newly produced dopamine (DA) on striatal DA receptors. In contrast to this view, recent studies in the rat model of Parkinson's disease point to the substantia nigra pars reticulata as an important target for the behavioral effects of l-DOPA. In the present study, we tested the contribution of the substantia nigra vs. that of the striatum, in the expression of contralateral turning induced by l-DOPA in rats with unilateral dopaminergic depletion. Rats turned contralaterally to the lesion in response to either intrastriatal or systemic l-DOPA administration. Injections of lidocaine into the denervated striatum substantially decreased, and occasionally completely abolished, the contralateral turning after systemic l-DOPA. These findings indicate that activation of the DA depleted striatum is both sufficient and essential for the expression of behavioral response after systemic administration of l-DOPA. The contribution of the substantia nigra to this behavioral response seems to depend to a great extent on an active striatal outflow.
传统观点认为,左旋多巴(l-DOPA)对帕金森病患者的行为影响是通过新生成的多巴胺(DA)作用于纹状体DA受体来实现的。与这一观点相反,最近在帕金森病大鼠模型中的研究指出,黑质网状部是l-DOPA行为效应的重要靶点。在本研究中,我们测试了在单侧多巴胺能缺失的大鼠中,黑质与纹状体在l-DOPA诱导的对侧旋转表达中的作用。无论是纹状体内注射还是全身注射l-DOPA,大鼠都会向损伤对侧旋转。向去神经支配的纹状体注射利多卡因可显著减少,偶尔完全消除全身注射l-DOPA后的对侧旋转。这些发现表明,全身注射l-DOPA后,DA缺失纹状体的激活对于行为反应的表达既是充分的也是必要的。黑质对这种行为反应的作用似乎在很大程度上取决于活跃的纹状体传出。