Dopamine dysregulation of movement control in L-DOPA-induced dyskinesia

The nigrostriatal dopamine (DA) system has an essential role in the selection and control of movement sequences, and its degeneration causes the characteristic motor symptoms of Parkinson's disease. Parkinsonian motor symptoms are alleviated by L-DOPA, but this treatment induces motor fluctuations and dyskinesias (abnormal involuntary movements). Clinical and experimental findings indicate that the motor complications of L-DOPA pharmacotherapy are triggered by transient and large changes in extracellular DA levels. The disruption of presynaptic DA homeostasis sets in motion a cascade of postsynaptic alterations, which prime the brain for a complicated motor response to dopaminomimetic treatment. L-DOPA-induced dyskinesia provides a paradigm to study how the dysregulation of DA release and clearance results in maladaptive neuroplasticity sustaining abnormal patterns of movement.