Dopamine transporter relation to dopamine turnover in Parkinson's disease
 

(related links following abstract are also very interesting.)

Ann Neurol. 2007 Sep 20; [Epub ahead of print] Links
Dopamine transporter relation to dopamine turnover in Parkinson's disease: a positron emission tomography study.Sossi V, de la Fuente-Fernández R, Schulzer M, Troiano AR, Ruth TJ, Stoessl AJ.
University of British Columbia, Vancouver, British Columbia, Canada.

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.

PMID: 17886297 [PubMed - as supplied by publisher]

Related LinksAge-related differences in levodopa dynamics in Parkinson's: implications for motor complications. [Brain. 2006][11C]DTBZ-PET correlates of levodopa responses in asymmetric Parkinson's disease. [Brain. 2003]Oral methylphenidate fails to elicit significant changes in extracellular putaminal dopamine levels in Parkinson's disease patients: positron emission tomographic studies. [Mov Disord. 2006]Clinical correlates of levodopa-induced dopamine release in Parkinson disease: a PET study. [Neurology. 2006]Levodopa-induced changes in synaptic dopamine levels increase with progression of Parkinson's disease: implications for dyskinesias. [Brain. 2004]See all Related Articles...