Floel A, Garraux G, Xu B, Breitenstein C, Knecht S, Herscovitch P, Cohen L G
Human Cortical Physiology Section, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, USA.
Neurobiol Aging. 2008 Feb;29(2):267-79. doi: 10.1016/j.neurobiolaging.2006.10.009. Epub 2006 Nov 13.
Normal aging is associated with a decrease in dopaminergic function and a reduced ability to form new motor memories with training. This study examined the link between both phenomena. We hypothesized that levodopa would (a) ameliorate aging-dependent deficits in motor memory formation, and (b) increase dopamine availability at the dopamine type 2-like (D2) receptor during training in task-relevant brain structures. The effects of training plus levodopa (100mg, plus 25mg carbidopa) on motor memory formation and striatal dopamine availability were measured with [(11)C]raclopride (RAC) positron emission tomography (PET). We found that levodopa did not alter RAC-binding potential at rest but it enhanced training effects on motor memory formation as well as dopamine release in the dorsal caudate nucleus. Motor memory formation during training correlated with the increase of dopamine release in the caudate nucleus. These results demonstrate that levodopa may ameliorate dopamine deficiencies in the elderly by replenishing dopaminergic presynaptic stores, actively engaged in phasic dopamine release during motor training.
正常衰老与多巴胺能功能下降以及通过训练形成新运动记忆的能力降低有关。本研究探讨了这两种现象之间的联系。我们假设左旋多巴会(a)改善与衰老相关的运动记忆形成缺陷,以及(b)在与任务相关的脑结构训练期间增加多巴胺2型(D2)受体处的多巴胺可用性。使用[(11)C]雷氯必利(RAC)正电子发射断层扫描(PET)测量训练加左旋多巴(100mg,加25mg卡比多巴)对运动记忆形成和纹状体多巴胺可用性的影响。我们发现左旋多巴在静息时不会改变RAC结合潜能,但它增强了训练对运动记忆形成的影响以及背侧尾状核中的多巴胺释放。训练期间的运动记忆形成与尾状核中多巴胺释放的增加相关。这些结果表明,左旋多巴可能通过补充多巴胺能突触前储备来改善老年人的多巴胺缺乏,这些储备在运动训练期间积极参与多巴胺的阶段性释放。