The neural mechanisms underlying levodopa-induced dyskinesia in Parkinson's disease

Treatment-related dyskinesias are the major limitation of dopamine replacem ent therapies such as levodopa in Parkinson's disease (PD). Recent studies in parkinsonian, nonhuman primates have highlighted abnormalities in neural functioning that might underlie the generation of dyskinetic symptoms in p atients with PD who have received prolonged dopaminergic therapy. This arti cle reviews studies on metabolic activity in subregions of the basal gangli a which suggest that profound abnormalities in basal ganglia output may und erlie levodopa-induced dyskinesia. Such abnormalities may result from chang es within basal ganglia circuitry and may include either overt changes in a verage firing rate or modulation of the pattern of cell-cell communication within subregions of the basal ganglia circuitry. An appreciation of abnorm alities in the mechanisms responsible for modulating synaptic transmission in the basal ganglia may suggest novel therapeutic approaches to the proble m of dyskinesia.