Post- versus presynaptic plasticity in L-DOPA-induced dyskinesia
Article first published online: 26 JUL 2006
Journal of Neurochemistry
Volume 99, Issue 2, pages 381–392, October 2006
How to Cite
Cenci, M. A. and Lundblad, M. (2006), Post- versus presynaptic plasticity in L-DOPA-induced dyskinesia. Journal of Neurochemistry, 99: 381–392. doi: 10.1111/j.1471-4159.2006.04124.x
- Issue published online: 26 JUL 2006
- Article first published online: 26 JUL 2006
- Received March 23, 2006; revised manuscript received June 18, 2006; accepted June 23, 2006.
- basal ganglia;
- blood-brain barrier;
- dopamine transporters;
- functional imaging;
- intracellular signaling;
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.