Dopamine-dependent motor learning: insight into levodopa's long-duration response.
Dopamine-dependent motor learning: insight into levodopa's long-duration response.
复制标题
DOI：
10.1002/ana.21947
复制
发表时间：
2010-05
影响因子：
11.2
通讯作者：
Zhuang, Xiaoxi
中科院分区：
文献类型：
--
作者：
Beeler, Jeff A.;Cao, Zhen Fang Huang;Kheirbek, Mazen A.;Ding, Yunmin;Koranda, Jessica;Murakami, Mari;Kang, Un Jung;Zhuang, Xiaoxi
多巴胺（DA）对运动表现、运动学习和皮质纹状体可塑性至关重要。然而，运动表现和学习之间的关系以及DA在其中的中介作用仍不清楚。为了研究这个问题，我们利用了PITx 3缺陷小鼠（无晶状体小鼠），其中背侧纹状体中的DA减少了90%。PITx 3缺陷小鼠在其笼中没有表现出明显的运动缺陷，但在需要新运动技能的运动任务中受损。我们使用加速旋转棒作为运动学习任务。我们发现PITx 3（−/−）中运动技能学习的缺陷是戏剧性的，可以通过左旋多巴治疗来挽救。此外，获得运动技能后停止左旋多巴治疗不会导致表现立即下降。相反，表现会逐渐下降，持续几天，这与左旋多巴的药代动力学无关。我们表明，这种逐渐下降是依赖于重新测试的经验。这一观察结果类似于对左旋多巴治疗的长期反应，在治疗开始后缓慢改善并逐渐退化。我们假设运动学习在帕金森病的病理学以及左旋多巴的治疗作用中可能发挥着重要的、未被充分认识的作用。我们认为，重要的，但神秘的长期反应，长期左旋多巴治疗是一种表现，挽救运动学习。
Dopamine (DA) is critical for motor performance, motor learning, and corticostriatal plasticity. The relationship between motor performance and learning, and the role of DA in the mediation of them, however, remain unclear. To examine this question, we took advantage of PITx3-deficient mice (aphakia mice), in which DA in the dorsal striatum is reduced by 90%. PITx3-deficient mice do not display obvious motor deficits in their home cage, but are impaired in motor tasks that require new motor skills. We used the accelerating rotarod as a motor learning task. We show that the deficiency in motor skill learning in PITx3(−/−) is dramatic and can be rescued with levodopa treatment. In addition, cessation of levodopa treatment after acquisition of the motor skill does not result in an immediate drop in performance. Instead, there is a gradual decline of performance that lasts for a few days, which is not related to levodopa pharmacokinetics. We show that this gradual decline is dependent on the retesting experience. This observation resembles the long-duration response to levodopa therapy in its slow buildup of improvement after the initiation of therapy and gradual degradation. We hypothesize that motor learning may play a significant, underappreciated role in the symptomatology of Parkinson disease as well as in the therapeutic effects of levodopa. We suggest that the important, yet enigmatic long-duration response to chronic levodopa treatment is a manifestation of rescued motor learning.
登录
查看更多内容
影响因子：
6.1
作者：
Ardayfio, Paul;Moon, JiSook;Kim, Kwang-Soo
通讯作者：
Kim, Kwang-Soo
影响因子：
11.2
作者：
Brooks, DJ
通讯作者：
Brooks, DJ
影响因子：
2.7
作者：
Kas, Martien J. H.;Van der Linden, Annemarie J. A.;Smidt, Marten P.
通讯作者：
Smidt, Marten P.
影响因子：
2.9
作者：
Ogura, T;Ogata, M;Saji, M
通讯作者：
Saji, M
影响因子：
9.9
作者：
Ghilardi, MF;Eidelberg, D;Ghez, C
通讯作者：
Ghez, C