To investigate the role of the dopamine transporter (DAT) in the regulation of synaptic dopamine (DA) levels in Parkinson's disease and its role in the preservation of DA in presynaptic terminals.

Ten Parkinson's disease patients (age, 62.9 ± 9.5 years; Unified Parkinson's Disease Rating Scale motor score in “off” state, 28.5 ± 8.2) underwent positron emission tomography with ¹¹C‐methylphenidate (MP, a DAT marker), ¹¹C‐dihydrotetrabenazine (a vesicular monoamine transporter 2 marker), and ¹⁸F‐fluorodopa, leading to the determination of the MP and ¹¹C‐dihydrotetrabenazine binding potentials (BPs) and the effective distribution volume for ¹⁸F‐fluorodopa, the inverse of DA turnover. Seven patients also underwent positron emission tomography with ¹¹C‐raclopride before and 1 hour after levodopa administration to estimate levodopa‐induced changes in synaptic DA concentration.

We found a significant positive correlation between effective distribution volume and BP_MP (r = 0.93; p < 0.001) and a significant negative correlation between changes in synaptic DA concentration and BP_MP (r = −0.93; p = 0.04), independent of disease severity and duration.

These data show that in Parkinson's disease, greater DAT levels are directly associated with lower DA turnover and lower changes in synaptic DA concentration. This implies that an important functional role of DAT is to maintain relatively constant synaptic DA levels and to preserve DA in nerve terminals. A decrease in DAT, although potentially serving as a compensatory mechanism in early disease, may ultimately result in increased DA turnover and higher oscillations in synaptic DA concentration, thereby possibly predisposing toward the occurrence of motor complications as disease progresses. Ann Neurol 2007