Effects of L-tryptophan on L-DOPA-induced dyskinesia in the L-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated macaque model of Parkinson’s disease.
Neuroscience Letters. 2014-04-01; 566: 72-76
DOI: 10.1016/j.neulet.2014.02.027
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1. Neurosci Lett. 2014 Apr 30;566:72-6. doi: 10.1016/j.neulet.2014.02.027. Epub 2014
Feb 23.
Effects of L-tryptophan on L-DOPA-induced dyskinesia in the
L-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated macaque model of
Parkinson’s disease.
Ko WK(1), Li Q(2), Bezard E(3).
Author information:
(1)Motac Neuroscience Ltd., Manchester, United Kingdom; Université de Bordeaux,
Institut des Maladies Neurodégénératives, UMR 5293, Bordeaux F-33000, France;
CNRS, Institut des Maladies Neurodégénératives, UMR 5293, Bordeaux F-33000,
France.
(2)Institute of Laboratory Animal Sciences, China Academy of Medical Sciences,
Beijing, China.
(3)Motac Neuroscience Ltd., Manchester, United Kingdom; Université de Bordeaux,
Institut des Maladies Neurodégénératives, UMR 5293, Bordeaux F-33000, France;
CNRS, Institut des Maladies Neurodégénératives, UMR 5293, Bordeaux F-33000,
France; Institute of Laboratory Animal Sciences, China Academy of Medical
Sciences, Beijing, China. Electronic address: .
In animal models of Parkinson’s disease (PD), the serotonergic
(5-hydroxytryptamine, 5-HT) system is thought to play an important
pathophysiological role in the development and expression of
l-3,4-dihydroxyphenylalanine (l-3,4-dihydroxyphenylalanine-DOPA)-induced
dyskinesia (LID). These abnormal involuntary movements are associated with the
unregulated release of dopamine from 5-HT fibres. Thus, modulating the false
neurotransmitter release from 5-HT neurons, via attuning the serotonin tone, may
be a potential therapeutic strategy in the treatment of LID. In this study, we
investigated the effects of the primary precursor of 5-HT, l-tryptophan, on LID
in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated macaques.
l-tryptophan treatment (0.5-5.0g) dramatically abolished the expression of LID.
However, this effect was associated with worsening of the therapeutic effects of
L-DOPA. These behavioural data further support the role of the serotonergic
system in expression of LID, highlighting the difficult challenge of targeting
5-HT neurons for alleviating dyskinesia and maintaining the therapeutic response
of L-DOPA.
Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
DOI: 10.1016/j.neulet.2014.02.027
PMID: 24572591 [Indexed for MEDLINE]