Reaction time and nigrostriatal dopamine function: the effects of age and practice
Reaction time and nigrostriatal dopamine function: the effects of age and practice
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DOI：
10.1016/0006-8993(88)90758-5
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发表时间：
1988-06
期刊：
影响因子：
2.9
通讯作者：
P. MacRae;W. Spirduso;R. Wilcox
中科院分区：
文献类型：
--
作者：
P. MacRae;W. Spirduso;R. Wilcox
正常的老年人和帕金森患者会随着黑质纹状体多巴胺（DA）系统的变化而迅速失去启动运动的能力（反应时间增加）。然而，这些人通过练习提高反应时间的能力还没有得到充分的评估。我们已经开发了一种啮齿类动物的人类反应时间模型，其中反应时间表现与黑质纹状体DA完整性的神经化学测量高度相关。在本报告中，15只年轻和10只年老的雄性Sprague-Dawley大鼠在反应时间任务中被训练为对外部刺激快速释放杠杆，以避免轻微的脚部电击。为了检验练习对这个反应时间任务的影响，幼龄动物在3、6和9月龄时接受5天的测试，老年动物在18、21和24月龄时接受5天的测试。从这个实践良好的任务中，测量了反应时间反应潜伏期，并将其与黑质纹状体DA功能（DA及其代谢物的稳态水平，D2DA受体亲和力和密度）的测量结果进行了比较。老年动物的反应潜伏期比年轻动物慢。然而，这些反应潜伏期的年龄差异在3个测试阶段中每个测试几天后消失，因此在每个测试阶段的第4天和第5天，老年动物的反应潜伏期没有明显慢于年轻动物。正如预期的那样，老年动物纹状体D2DA受体密度降低，但DA受体亲和力没有年龄差异。老龄动物的DA代谢率（二羟基苯乙酸和同型香草酸；DOPAC + HVA）显著高于幼龄动物。此外，各组间纹状体D2DA受体数量与反应潜伏期呈显著负相关。这种负相关表明反应潜伏期越快（越低）的动物纹状体D2DA受体的数量越多。这些数据表明，运动系统的可塑性可以通过广泛的练习来克服与年龄相关的反应时间障碍。反应时间似乎与黑质纹状体DA功能的多个方面有关。
Normal aged and Parkinsonian individuals lose the ability to initiate movements rapidly (increased reaction time) in parallel with changes in the nigrostriatal dopamine (DA) system. However, the ability of these individuals to improve their reaction time with practice has not been adequately assessed. We have developed a rodent model for human reaction time in which reaction time performance correlates highly with neurochemical measures of nigrostriatal DA integrity. In the present report, 15 young and 10 old male Sprague-Dawley rats were conditioned in a reaction time task to release a lever quickly in response to external stimuli in order to avoid a mild footshock. In order to examine the effects of practice on this reaction time task, the young animals were tested for 5 days at 3, 6 and 9 months of age and the old animals were tested for 5 days at 18, 21, and 24 months of age. From this well-practiced task, reaction time response latencies were measured and compared to measures of nigrostriatal DA function (steady-state levels of DA and its metabolites, D2DA receptor affinity and density). The old animals were slower in response latencies than the young animals. These age differences in response latencies, however, disappeared after several days of testing at each of the 3 test sessions, so that the old animals were not significantly slower than the young animals on days 4 and 5 of each session. As expected, the old animals showed reduced striatal D2DA receptor density with no age differences in DA receptor affinity. The old animals had significantly higher ratios of DA metabolities (dihydroxyphenylacetic acid and homovanillic acid; DOPAC + HVA) to DA than the young animals. Furthermore, across groups there was a significant negative correlation between striatal D2DA receptor numbers and response latencies. This negative correlation indicated that the animals with the faster (lower) response latencies had the higher number of striatal D2DA receptors. These data suggest that the plasticity of the motor system allows age-related impairments in reaction time to be overcome with extensive practice. It also appears that reaction time is related to multiple aspects of nigrostriatal DA function.