摘要：SummaryWith continued levodopa treatment, most patients with Parkinson disease (PD) develop levodopa-induced dyskinesias (LIDs)—abnormal involuntary movements (AIMs) characterized primarily by chorea. Clinically, LIDs depend on nigrostriatal degeneration and sensitization to repeated levodopa doses. However, the degree of dopamine denervation is correlated with levodopa-induced changes in striatal dopamine. Therefore, pulsatile dopamine release may induce AIMs independently of nigrostriatal degeneration. We optogenetically stimulated dopamine neurons in healthy rats as they engaged in skilled reaching. Repeated stimulation induced progressive AIMs whose severity was modified by behavioral context. AIMs were milder with stimulation during reaches, and more severe if stimulation occurred between reaches. Despite gradual induction, AIMs recurred immediately with subsequent dopamine neuron stimulation. Thus, nigrostriatal denervation is not necessary for fluctuating striatal dopamine to induce AIMs, and behavioral context modulates AIM expression. Furthermore, pulsatile dopamine release induces persistent changes in motor circuits that are revealed by subsequent dopamine neuron activation in appropriate contexts.Graphical abstractDisplay OmittedHighlights•Repeated dopamine neuron activation causes involuntary movements in healthy rats•These movements resemble levodopa-induced dyskinesias in parkinsonian rats•Movement severity depends on the history of prior stimulation•Movement severity is diminished in rats actively engaged in goal-directed behaviorBiological sciences; Behavioral neuroscience; Cellular neuroscience
