The treatment of motor symptoms of
Parkinson disease (PD) with the
dopamine (DA) precursor,
l-3,4-dihydroxyphenylalanine (
l-DOPA) introduced 50years ago still remains a very effective medication. However,
involuntary movements termed
l-DOPA-induced
dyskinesias (LID) appear in the vast majority of PD patients after chronic treatment and may become disabling. Once they appeared, the first dose after a several-weeks drug holiday will trigger them again, showing that
l-DOPA has permanently or persistently modified the brain response to DA. LID are very difficult to manage and no drug is yet approved for
dyskinesias, aside from a modest benefit with
amantadine. New drugs are needed for PD to alleviate parkinsonian symptoms without inducing
dyskinesias. Hence, animal models have been developed to seek the mechanisms involved in LID and new drug targets. The
neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (
MPTP) was discovered as a contamination of a derivative of
heroin taken by drug users and produced similar motor symptoms as idiopathic PD. Since then,
MPTP is used extensively to model PD and LID in non-human primates and mice in addition to the classical PD model in rats with a
6-hydroxydopamine (6-OHDA) lesion. This article reviews rodent and non-human primate models of PD that reproduce motor complications induced by DA replacement
therapy. Moreover, key biochemical changes in the brain of post-mortem PD patients with LID will be compared to those observed in animal models. Finally, the translational usefulness of drugs found to treat LID in animal models will be compared to their clinical activities.