Wallenberg Neuroscience Center, Division of Neurobiology, Department of Experimental Medical Science, Lund University, Lund 221 84, Sweden.
Neurosci Res. 2012 Jun;73(2):168-72. doi: 10.1016/j.neures.2012.03.004. Epub 2012 Mar 17.
The present study investigated whether the rotation rate induced by amphetamine in 6-OHDA-lesioned rats was predictive of development of L-DOPA-induced dyskinesia (LID) and success of the lesion procedure in our experimental settings. We collected data from 312 6-OHDA-lesioned rats (from different sets of experiments). Rats were subjected to the amphetamine-induced rotation test (2.5mg/kg) and chronically treated with L-DOPA (6 mg/kg) to establish dyskinesia. A poor correlation was present between amphetamine-induced rotation and LID. Moreover, no correlation was found between amphetamine-induced rotation and tyrosine hydroxylase (TH) positive cell number in the lesioned substantia nigra pars compacta, while there was a weak correlation between the percentage of TH positive cell number and LID. These results indicate that the amphetamine-induced rotation test is a poor predictor of the 6-OHDA-lesion success, as well as of the development of LID at the dose of amphetamine used here. Our data also suggest that all rats with amphetamine-induced rotation ≥ 3 turns/min should be included in dyskinesia studies, as they showed the same propensity to develop dyskinesia. Moreover, SERT expression levels suggest that reduced striatal and pallidal serotonin innervation might have contributed to the lower dyskinesia levels observed in a subset of amphetamine-responsive rats.
本研究旨在探讨安非他命诱导的旋转率是否能预测 6-OHDA 损伤大鼠发展为 L-DOPA 诱导的运动障碍（LID），以及在我们的实验环境中损伤程序的成功。我们从 312 只 6-OHDA 损伤大鼠（来自不同的实验集）中收集数据。大鼠接受安非他命诱导的旋转测试（2.5mg/kg）和慢性 L-DOPA（6mg/kg）治疗以建立运动障碍。安非他命诱导的旋转与 LID 之间存在较差的相关性。此外，安非他命诱导的旋转与损伤的黑质致密部酪氨酸羟化酶（TH）阳性细胞数之间没有相关性，而 TH 阳性细胞数的百分比与 LID 之间存在弱相关性。这些结果表明，安非他命诱导的旋转测试是 6-OHDA 损伤成功以及在此使用的安非他命剂量下发展为 LID 的不良预测指标。我们的数据还表明，所有安非他命诱导的旋转≥3 转/分钟的大鼠都应纳入运动障碍研究，因为它们表现出相同的易发性发展为运动障碍。此外，SERT 表达水平表明，纹状体和苍白球中 5-羟色胺神经支配减少可能导致一部分对安非他命有反应的大鼠观察到较低的运动障碍水平。
