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
- PMID: 24572591
- DOI: 10.1016/j.neulet.2014.02.027
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
Abstract
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.
Keywords: 5-HT; 5-Hydroxytryptamine; Parkinson's disease; Serotonin; l-DOPA-induced dyskinesia; l-Tryptophan.
Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
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