The role of neuroplasticity in dopaminergic therapy for Parkinson disease

Xiaoxi Zhuang, Pietro Mazzoni, Un Jung Kang

Research output: Contribution to journalReview articlepeer-review

42 Scopus citations

Abstract

Dopamine replacement is a mainstay of therapeutic strategies for Parkinson disease (PD). The motor response to therapy involves an immediate improvement in motor function, known as the short-duration response (SDR), followed by a long-duration response (LDR) that develops more slowly, over weeks. Here, we review evidence in patients and animal models suggesting that dopamine-dependent corticostriatal plasticity, and retention of such plasticity in the absence of dopamine, are the mechanisms underlying the LDR. Conversely, experience-dependent aberrant plasticity that develops slowly under reduced dopamine levels could contribute substantially to PD motor symptoms before initiation of dopamine replacement therapy. We place these findings in the context of the role of dopamine in basal ganglia function and corticostriatal plasticity, and provide a new framework suggesting that therapies that enhance the LDR could be more effective than those targeting the SDR. We further propose that changes in neuroplasticity constitute a form of disease modification that is distinct from prevention of degeneration, and could be responsible for some of the unexplained disease-modifying effects of certain therapies. Understanding such plasticity could provide novel therapeutic approaches that combine rehabilitation and pharmacotherapy for treatment of neurological and psychiatric disorders involving basal ganglia dysfunction.

Original languageEnglish
Pages (from-to)248-256
Number of pages9
JournalNature Reviews Neurology
Volume9
Issue number5
DOIs
StatePublished - May 1 2013
Externally publishedYes

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