Dopamine replacement via L-Dopa is the main current therapeutic strategy for Parkinson’s disease. 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.
In this review, Zhuang and colleagues discuss evidence suggesting that dopamine-dependent corticostriatal plasticity is involved in the mechanisms underlying long-duration response. Conversely, experience-dependent aberrant plasticity that develops slowly under reduced dopamine levels could contribute substantially to Parkinson motor symptoms before initiation of dopamine replacement therapy. The authors 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.
They propose that changes in neuroplasticity represent modifications that are distinct from prevention of degeneration, and could be responsible for some of the unexplained disease-modifying effects of certain therapies. The authors suggest that such plasticity could provide novel therapeutic approaches combining rehabilitation and pharmacotherapy for treatment of brain disorders involving basal ganglia dysfunction.
Zhuang X, Mazzoni P, Kang UJ: The role of neuroplasticity in dopaminergic therapy for Parkinson disease. Nature Rev. Neurol. 9(5): 248-256 (2013).
