Dopamine transporter binding is unaffected by L-DOPA administration in normal and MPTP-treated monkeys.
BACKGROUND
Radiotracer imaging of the presynaptic nigrostriatal dopaminergic system is used to assess disease progression in Parkinson's disease (PD) and may provide a useful adjunct to clinical assessment during therapeutic trials of potential neuroprotective agents. Several clinical trials comparing dopamine agonists to L-DOPA or early vs. late L-DOPA have revealed differences between clinical assessment and imaging of the presynaptic dopaminergic system, hence questioning the comparability of these measures as neuroprotection outcome variables. Thus, results of these studies may have been affected by factors other than the primary biological process investigated.


RESULTS
We tested the possibility that L-DOPA might interfere with DAT binding. Post-mortem DAT binding was conducted in normal and MPTP-treated macaque monkeys that were administered L-DOPA, acutely or chronically. In parallel, DAT SPECT was conducted in MPTP-treated animals that were administered chronic L-DOPA. [99mTc]TRODAT-1 SPECT binding was similarly reduced in all MPTP monkeys regardless of L-DOPA treatment. L-DOPA had no significant effect on post-mortem DAT binding either in saline or in MPTP-lesioned animals.


CONCLUSIONS
These data indicate that L-DOPA does not induce modifications of DAT expression detectable by SPECT of by DAT binding autoradiography, suggesting that differences between clinical assessment and radiotracer imaging in clinical trials may not be specifically related to L-DOPA treatment.
Université Victor Segalen-Bordeaux 2, Centre National de la Recherche Scientifique, Bordeaux Institute of Neuroscience, UMR 5227, Bordeaux, France. pierre-olivier.fernagut@u-bordeaux2.fr
Pierre-Olivier
PO
Fernagut
Qin
Q
Li
Sandra
S
Dovero
Piu
P
Chan
Tao
T
Wu
Paula
P
Ravenscroft
Michael
M
Hill
Zhenwen
Z
Chen
Erwan
E
Bezard
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D000978:Antiparkinson Agents / Q000008:administration & dosage / Q000494:pharmacology; D001345:Autoradiography; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism*; D005260:Female; D007980:Levodopa / Q000008:administration & dosage / Q000494:pharmacology*; D008253:Macaca mulatta; D010302:Parkinson Disease, Secondary / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D011485:Protein Binding / Q000187:drug effects*; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods
D000978:Antiparkinson Agents; D050483:Dopamine Plasma Membrane Transport Proteins; D007980:Levodopa; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine