Metz G A, Farr T, Ballermann M, Whishaw I Q
Department of Psychology and Neuroscience, University of Lethbridge, 4401 University Drive, Lethbridge, AB, Canada, T1K 3M4.
Eur J Neurosci. 2001 Jul;14(1):27-37. doi: 10.1046/j.0953-816x.2001.01615.x.
L-dopa therapy reverses some but not all of the motor deficits in human Parkinson patients. Although a number rat analogues of human Parkinson's disease have been developed for evaluating the efficacy of drug therapies, it is not known whether L-dopa has a similar selective action on the motor symptoms in the rat models. To examine the effectiveness of L-dopa in reversing the motor deficits in rats, we administered 6-OHDA unilaterally to produce hemi-Parkinson rats, which were then trained to reach for food using either their impaired (contralateral to the lesion) limb or their good (ipsilateral to the lesion) limb. To assess the skill, accuracy and range of limb movement, rats reached for pasta from a horizontal array of 260 vertically orientated pieces of pasta. The number and location of pasta pieces taken from this matrix was calculated and the qualitative aspects of the reaching movements were rated. The quantitative data on pasta sticks retrieved indicated that forelimb extension and movement radius around the shoulder joint was reduced by 6-OHDA treatment and did not improve after chronic L-dopa treatment. The qualitative analysis showed that grasping patterns, paw movements and body movements impaired by the lesion were also not improved by L-dopa treatment. These findings are the first in the rat to suggest that whereas L-dopa has a general activating effect on the rat's whole-body movements, as displayed in contralateral rotation, its effectiveness does not extend to skilled forelimb movements. The results are discussed in relationship to the idea that the restoration of some skilled movements may require normal synaptic function.
左旋多巴疗法可逆转人类帕金森病患者的部分而非全部运动功能障碍。尽管已经开发出一些人类帕金森病的大鼠类似模型来评估药物治疗的疗效,但尚不清楚左旋多巴在大鼠模型中对运动症状是否具有类似的选择性作用。为了研究左旋多巴逆转大鼠运动功能障碍的有效性,我们单侧注射6-羟基多巴胺(6-OHDA)制备偏侧帕金森大鼠,然后训练它们用受损(损伤对侧)肢体或完好(损伤同侧)肢体抓取食物。为了评估肢体运动的技巧、准确性和范围,大鼠从由260根垂直排列的意大利面条组成的水平阵列中抓取面条。计算从这个矩阵中抓取的面条数量和位置,并对抓取动作的定性方面进行评分。关于抓取面条的定量数据表明,6-OHDA处理会使前肢伸展和肩关节周围的运动半径减小,慢性左旋多巴治疗后并未改善。定性分析表明,左旋多巴治疗也不能改善因损伤而受损的抓握模式、爪子运动和身体运动。这些发现首次表明,尽管左旋多巴对大鼠的全身运动具有普遍的激活作用,如对侧旋转所示,但其有效性并不扩展到熟练的前肢运动。结合恢复某些熟练运动可能需要正常突触功能这一观点对结果进行了讨论。