Dopamine transporter relation to dopamine turnover in Parkinson's disease: a positron emission tomography study.
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.


CONCLUSIONS
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.
Sossi
Vesna
V
University of British Columbia, Vancouver, British Columbia, Canada. vesna@physics.ubc.ca
de la Fuente-Fernández
Raúl
R
Schulzer
Michael
M
Troiano
Andre R
AR
Ruth
Thomas J
TJ
Stoessl
A Jon
AJ
D000368:Aged; D004298:Dopamine / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000175:diagnosis / Q000378:metabolism*; D049268:Positron-Emission Tomography / Q000379:methods; D017729:Presynaptic Terminals / Q000378:metabolism; D011485:Protein Binding / Q000502:physiology
D050483:Dopamine Plasma Membrane Transport Proteins; D004298:Dopamine