title: 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.
authors.affiliation: 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.
authors.forename: Wai Kin D
authors.initials: WK
authors.lastname: Ko
authors.affiliation: Institute of Laboratory Animal Sciences, China Academy of Medical Sciences, Beijing, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Li
authors.affiliation: 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: erwan.bezard@u-bordeaux2.fr.
authors.forename: Erwan
authors.initials: E
authors.lastname: Bezard
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D000978:Antiparkinson Agents / Q000009:adverse effects* / Q000627:therapeutic use; D003342:Corpus Striatum / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D004409:Dyskinesia, Drug-Induced / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D005260:Female; D007980:Levodopa / Q000009:adverse effects* / Q000627:therapeutic use; D008252:Macaca fascicularis; D009043:Motor Activity / Q000187:drug effects; D010300:Parkinson Disease / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D014364:Tryptophan / Q000494:pharmacology*
chemical_list: D000978:Antiparkinson Agents; D007980:Levodopa; D014364:Tryptophan; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D004298:Dopamine
keywords: 5-HT; 5-Hydroxytryptamine; Parkinson's disease; Serotonin; l-DOPA-induced dyskinesia; l-Tryptophan