Departments of Molecular & Integrative Physiology, University of Kansas Medical Center, Kansas City, KS 66160, United States.
Behav Brain Res. 2011 Nov 20;225(1):97-103. doi: 10.1016/j.bbr.2011.07.002. Epub 2011 Jul 8.
Deficits in manual motor control often accompany the early stages of Parkinson's disease (PD), and are often revealed through isometric force tasks. In order to determine whether similar deficits occur in a rat model of early-stage PD, young (8 months) and middle-aged (18 months) rats were trained to produce sustained press-hold-release isometric forelimb responses that allowed for analyses of force output and spectral analysis of forelimb stability and tremor. Rats then received a 6-hydroxydopamine (6-OHDA) infusion into the striatum contralateral to the trained forelimb and were tested for 4 weeks post-lesion. The resulting partial striatal dopamine depletions (which at 41±12% and 43±6% in young and middle-aged rats, respectively, did not differ between the two groups) resulted in isometric forelimb deficits. Specifically, rats exhibited significantly diminished force stability and increased high frequency (10-25Hz) tremor, indicating potential postural disturbances and increased postural tremor, respectively. Durations of press-hold-release bouts were also increased post-lesion, suggesting difficulty in task disengagement. Despite pre-lesion differences in some of the force measures, the effects of partial nigrostriatal DA depletion did not differ between the two age groups. These results support the use of the press-while-licking task in preclinical studies modeling isometric force control deficits in PD.
手部运动控制缺陷常伴随帕金森病（PD）的早期阶段出现，通常可通过等长力量任务来揭示。为了确定在早期 PD 大鼠模型中是否存在类似的缺陷，年轻（8 个月）和中年（18 个月）大鼠接受了训练，以产生持续的按压-保持-释放等长前肢反应，从而可以分析力输出以及前肢稳定性和震颤的频谱分析。然后，大鼠在前肢训练对侧纹状体中接受了 6-羟基多巴胺（6-OHDA）输注，并在损伤后 4 周进行了测试。结果导致纹状体多巴胺部分耗竭（在年轻和中年大鼠中分别为 41±12%和 43±6%，两组之间没有差异）导致等长前肢缺陷。具体来说，大鼠表现出明显的力稳定性降低和高频（10-25Hz）震颤增加，分别表明潜在的姿势障碍和增加的姿势震颤。损伤后按压-保持-释放回合的持续时间也增加，表明任务脱离困难。尽管在一些力测量方面存在损伤前差异，但部分黑质纹状体 DA 耗竭的影响在两个年龄组之间没有差异。这些结果支持在临床前研究中使用按压舔舐任务来模拟 PD 中的等长力量控制缺陷。
