Background Serotonergic mechanisms play a key role in the development of the Levodopa-induced dyskinesias (LIDs) in patients with Parkinson's disease (PD). We hypothesised that an unfavourable serotonin-to-dopamine terminal ratio in the putamen would be most detrimental in dyskinetic patients. We investigated the role of serotonin-to-dopamine transporter binding ratios in the development of dyskinesias in Parkinson's disease patients.

Methods/Subjects Twenty-eight Parkinson's disease patients[17 with LIDs;11 stable] and 12 age and gender-matched healthy controls were studied with [11C]DASB PET and [123I]FP-CIT SPECT, Imaging. We have employed a simplified reference tissue model using cerebellar reference for the quantification of [11C]DASB, whereas a semi-quantification approach was used for [123I]FP-CIT. We estimated uptake values in the putamen.

Results Parkinson's disease patients showed decreases in [123I]FP-CIT binding (p<0.001) compared to controls, 51% in the stable and 62% in the LIDs group. PD patients showed decreases in [11C]DASB binding (p<0.01), but there were no differences between the stable (37% loss) and LIDs(31% loss) groups. PD patients with LIDs had 103% increased [11C]DASB-to-[123I]FP-CIT binding ratio, whereas in the PD stable group the ratio was increased by 76%, relative to HCs. Higher [11C]DASB-to-[123I]FP-CIT binding ratio correlated with longer disease duration for the 28 PD patients (r=0.52;p<0.01).

Conclusion SERT-to-DAT ratio increases as PD progresses and patients experience LIDs.