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Dopamine transporter relation to dopamine turnover in Parkinson's disease: a positron emission tomography study
Author(s) -
Sossi Vesna,
de la FuenteFernández Raúl,
Schulzer Michael,
Troiano Andre R.,
Ruth Thomas J.,
Stoessl A. Jon
Publication year - 2007
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.21204
Subject(s) - dopamine transporter , dopamine , positron emission tomography , parkinson's disease , vesicular monoamine transporter 2 , medicine , levodopa , endocrinology , dopaminergic , neuroscience , psychology , disease
Objective 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. Methods 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 11 C‐methylphenidate (MP, a DAT marker), 11 C‐dihydrotetrabenazine (a vesicular monoamine transporter 2 marker), and 18 F‐fluorodopa, leading to the determination of the MP and 11 C‐dihydrotetrabenazine binding potentials (BPs) and the effective distribution volume for 18 F‐fluorodopa, the inverse of DA turnover. Seven patients also underwent positron emission tomography with 11 C‐raclopride before and 1 hour after levodopa administration to estimate levodopa‐induced changes in synaptic DA concentration. Results 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. Interpretation 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