title: The role of neuroplasticity in dopaminergic therapy for Parkinson disease.
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.
authors.affiliation: Department of Neurobiology, University of Chicago Medicine and Biological Sciences, 947 South 58th Street, MC 0926, Chicago, IL 60637, USA.
authors.forename: Xiaoxi
authors.initials: X
authors.lastname: Zhuang
authors.forename: Pietro
authors.initials: P
authors.lastname: Mazzoni
authors.forename: Un Jung
authors.initials: UJ
authors.lastname: Kang
mesh_terms: D000818:Animals; D015259:Dopamine Agents / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D009473:Neuronal Plasticity / Q000187:drug effects* / Q000502:physiology*; D010300:Parkinson Disease / Q000188:drug therapy*
chemical_list: D015259:Dopamine Agents