The crucial role of
dopamine (DA) in movement control is illustrated by the spectrum of
motor disorders caused by either a deficiency or a hyperactivity of dopaminergic transmission in the basal ganglia. The degeneration of nigrostriatal DA neurons in
Parkinson's disease causes poverty and slowness of movement. These symptoms are greatly improved by pharmacological DA replacement with L-3,4-dihydroxy-phenylalanine (
L-DOPA), which however causes excessive
involuntary movements in a majority of patients.
L-DOPA-induced
dyskinesia (abnormal
involuntary movements) provides a topic of investigation at the interface between clinical and basic neuroscience. In this article, we review recent studies in rodent models, which have uncovered two principal alterations at the basis of the
movement disorder, namely, an abnormal pre-synaptic handling of exogenous
L-DOPA, and a hyper-reactive post-synaptic response to DA. Dysregulated nigrostriatal DA transmission causes secondary alterations in a variety of non-dopaminergic transmitter systems, the manipulation of which modulates
dyskinesia through mechanisms that are presently unclear. Further research on
L-DOPA-induced
dyskinesia will contribute to a deeper understanding of the functional interplay between
neurotransmitters and
neuromodulators in the motor circuits of the basal ganglia.