L-DOPA-induced dyskinesia, is striatal dopamine depletion a requisite?

• High dose L-DOPA may elicit dyskinesia in normal primates.
• High dose L-DOPA may elicit dyskinesia in non-Parkinsonian human subjects.
• Striatal dopamine denervation may not be a requisite to dyskinesia development.

l-3,4-Dihydroxyphenylalanine (L-DOPA) is currently the most effective drug available to treat the symptoms of Parkinson's disease (PD). A limitation is that chronic administration of L-DOPA almost invariably, but not universally, leads to the development of abnormal involuntary movements, dyskinesia. Research suggests that striatal dopamine depletion is an important aetiological factor leading to dyskinesia development. However, in studies where L-DOPA was administered to normal animals and human subjects not afflicted by PD, abnormal involuntary movements were sometimes elicited. These studies are reviewed here and their potential significance for the pathophysiology of dyskinesia is discussed. It is concluded that, if striatal dopamine depletion may not be a requisite for the development of dyskinesia, it probably acts as a permissive factor, at least with the doses commonly employed in the clinic.