Dopamine‐dependent motor learning: Insight into levodopa's long‐duration response
Identifieur interne : 000739 ( Main/Exploration ); précédent : 000738; suivant : 000740Dopamine‐dependent motor learning: Insight into levodopa's long‐duration response
Auteurs : Jeff A. Beeler [États-Unis] ; Zhen Fang Huang Cao [États-Unis] ; Mazen A. Kheirbek [États-Unis] ; Yunmin Ding [États-Unis] ; Jessica Koranda [États-Unis] ; Mari Murakami [États-Unis] ; Un Jung Kang [États-Unis] ; Xiaoxi Zhuang [États-Unis]Source :
- Annals of Neurology [ 0364-5134 ] ; 2010-05.
Abstract
Objective: 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. Methods: 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. Results: 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. Interpretation: 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. ANN NEUROL 2010;67:639–647
Url:
DOI: 10.1002/ana.21947
Affiliations:
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The relationship between motor performance and learning, and the role of DA in the mediation of them, however, remain unclear. Methods: 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. Results: 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. Interpretation: 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. ANN NEUROL 2010;67:639–647</div></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Illinois</li><li>État de New York</li></region></list><tree><country name="États-Unis"><region name="Illinois"><name sortKey="Beeler, Jeff A" sort="Beeler, Jeff A" uniqKey="Beeler J" first="Jeff A." last="Beeler">Jeff A. Beeler</name></region><name sortKey="Cao, Zhen Fang Huang" sort="Cao, Zhen Fang Huang" uniqKey="Cao Z" first="Zhen Fang Huang" last="Cao">Zhen Fang Huang Cao</name><name sortKey="Ding, Yunmin" sort="Ding, Yunmin" uniqKey="Ding Y" first="Yunmin" last="Ding">Yunmin Ding</name><name sortKey="Kang, Un Jung" sort="Kang, Un Jung" uniqKey="Kang U" first="Un Jung" last="Kang">Un Jung Kang</name><name sortKey="Kang, Un Jung" sort="Kang, Un Jung" uniqKey="Kang U" first="Un Jung" last="Kang">Un Jung Kang</name><name sortKey="Kheirbek, Mazen A" sort="Kheirbek, Mazen A" uniqKey="Kheirbek M" first="Mazen A." last="Kheirbek">Mazen A. Kheirbek</name><name sortKey="Kheirbek, Mazen A" sort="Kheirbek, Mazen A" uniqKey="Kheirbek M" first="Mazen A." last="Kheirbek">Mazen A. Kheirbek</name><name sortKey="Koranda, Jessica" sort="Koranda, Jessica" uniqKey="Koranda J" first="Jessica" last="Koranda">Jessica Koranda</name><name sortKey="Murakami, Mari" sort="Murakami, Mari" uniqKey="Murakami M" first="Mari" last="Murakami">Mari Murakami</name><name sortKey="Zhuang, Xiaoxi" sort="Zhuang, Xiaoxi" uniqKey="Zhuang X" first="Xiaoxi" last="Zhuang">Xiaoxi Zhuang</name><name sortKey="Zhuang, Xiaoxi" sort="Zhuang, Xiaoxi" uniqKey="Zhuang X" first="Xiaoxi" last="Zhuang">Xiaoxi Zhuang</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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