Post- versus presynaptic plasticity in L-DOPA-induced dyskinesia.
L-3,4-dihydroxyphenylalanine (L-DOPA) remains the most efficacious drug for the treatment of Parkinson's disease (PD), but causes adverse effects that limit its utility. L-DOPA-induced dyskinesia (abnormal involuntary movements) is a significant clinical problem that attracts growing scientific interest. Current notions attribute the development of dyskinesia to two main factors, viz. the loss of nigrostriatal dopamine (DA) projections and the maladaptive changes produced by L-DOPA at sites postsynaptic to the nigrostriatal neuron. Basic research in the past 15 years has placed a lot of emphasis on the postsynaptic plasticity associated with dyskinesia, but recent experimental work shows that also some presynaptic factors, involving the regulation of L-DOPA/DA release and metabolism in the brain, may show plasticity during treatment. This review summarizes significant studies of L-DOPA-induced dyskinesia in patients and animal models, and outlines directions for future experiments addressing mechanisms of presynaptic plasticity. These investigations may uncover clues to the varying susceptibility to L-DOPA-induced dyskinesia among PD patients, paving the way for tailor-made treatments.
Cenci
M Angela
MA
Department of Experimental Medical Science, Basal Ganglia Pathophysiology Unit, Lund University, BMC F11, S.221 84 Lund, Sweden. Angela.Cenci_Nilsson@med.lu.se
Lundblad
Martin
M
D000818:Animals; D001479:Basal Ganglia / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D015259:Dopamine Agents / Q000009:adverse effects*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000187:drug effects / Q000378:metabolism; D004409:Dyskinesia, Drug-Induced / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D007980:Levodopa / Q000009:adverse effects*; D009473:Neuronal Plasticity / Q000187:drug effects* / Q000502:physiology; D013569:Synapses / Q000187:drug effects* / Q000378:metabolism; D009435:Synaptic Transmission / Q000502:physiology
D015259:Dopamine Agents; D050483:Dopamine Plasma Membrane Transport Proteins; D007980:Levodopa; D004298:Dopamine