Effects of l-tryptophan on l-DOPA-induced dyskinesia in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated macaque model of Parkinson's disease

•l-tryptophan treatment abolished established dyskinesia in MPTP macaque.•Locomotor activity reduction suggests an anti-dyskinetic and an anti-l-DOPA action.•Reduction of good on-time confirms l-tryptophan interferes with l-DOPA effects. 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.