Journal article

Differential Dopamine Receptor Occupancy Underlies L-DOPA-Induced Dyskinesia in a Rat Model of Parkinson's Disease

Gurdal Sahin, Lachlan H Thompson, Sonia Lavisse, Merve Ozgur, Latifa Rbah-Vidal, Frederic Dolle, Philippe Hantraye, Deniz Kirik

PLOS ONE | PUBLIC LIBRARY SCIENCE | Published : 2014

Abstract

Dyskinesia is a major side effect of an otherwise effective L-DOPA treatment in Parkinson's patients. The prevailing view for the underlying presynaptic mechanism of L-DOPA-induced dyskinesia (LID) suggests that surges in dopamine (DA) via uncontrolled release from serotonergic terminals results in abnormally high level of extracellular striatal dopamine. Here we used high-sensitivity online microdialysis and PET imaging techniques to directly investigate DA release properties from serotonergic terminals both in the parkinsonian striatum and after neuronal transplantation in 6-OHDA lesioned rats. Although L-DOPA administration resulted in a drift in extracellular DA levels, we found no evide..

View full abstract

Grants

Awarded by Swedish Research Council


Awarded by Swedish Parkinson Foundation


Awarded by European Research Council (ERC)


Awarded by European Union


Funding Acknowledgements

The authors would like to acknowledge the Swedish Research Council (K2009-61P-20945-03-1), Swedish Parkinson Foundation (grant no. 334/10), the European Research Council (ERC) Starting Grant (TreatPD, 242932) and European Union 6th Framework Program project Diagnostic Molecular Imaging (DiMI, LSHB-CT-2005-512146). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.