Contribution of pre-synaptic mechanisms to l-DOPA-induced dyskinesia

Positron emission tomography (PET) imaging studies have shown that peak-dose dyskinesia is associated to abnormally high levels of synaptic dopamine (DA) in the caudate-putamen of dyskinetic L-DOPA-treated patients. High striatal extracellular DA levels have also been found in dyskinetic 6-OHDA-lesioned rats as compared to non-dyskinetic ones, suggesting that extracellular DA levels may play a key role in the induction of dyskinesia. In this article we review the evidences pointing to the serotonin system as the primary cause for the abnormally high levels of L-DOPA-derived extracellular DA in Parkinson's disease, and we discuss the feasibility of a therapeutic approach targeting this system.