Dopamine transporter binding is unaffected by L-DOPA administration in normal and MPTP-treated monkeys.
PLoS ONE. 2010-11-22; 5(11): e14053
DOI: 10.1371/journal.pone.0014053
Lire sur PubMed
1. PLoS One. 2010 Nov 22;5(11):e14053. doi: 10.1371/journal.pone.0014053.
Dopamine transporter binding is unaffected by L-DOPA administration in normal and
MPTP-treated monkeys.
Fernagut PO(1), Li Q, Dovero S, Chan P, Wu T, Ravenscroft P, Hill M, Chen Z,
Bezard E.
Author information:
(1)Université Victor Segalen-Bordeaux 2, Centre National de la Recherche
Scientifique, Bordeaux Institute of Neuroscience, UMR 5227, Bordeaux, France.
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.
METHODOLOGY/PRINCIPAL FINDINGS: 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/SIGNIFICANCE: 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.
DOI: 10.1371/journal.pone.0014053
PMCID: PMC2989907
PMID: 21124922 [Indexed for MEDLINE]