JOURNAL ARTICLE
RANDOMIZED CONTROLLED TRIAL

Abnormal bidirectional plasticity-like effects in Parkinson's disease

Ying-Zu Huang, John C Rothwell, Chin-Song Lu, Wen-Li Chuang, Rou-Shayn Chen
Brain 2011, 134 (Pt 8): 2312-20
21742734
Levodopa-induced dyskinesia is a major complication of long-term dopamine replacement therapy for Parkinson's disease that becomes increasingly problematic in advanced Parkinson's disease. Although the cause of levodopa-induced dyskinesias is still unclear, recent work in animal models of the corticostriatal system has suggested that levodopa-induced dyskinesias might result from abnormal control of synaptic plasticity. In the present study, we aimed to explore control of plasticity in patients with Parkinson's disease with and without levodopa-induced dyskinesias by taking advantage of a newly developed protocol that tests depotentiation of pre-existing long-term potentiation-like synaptic facilitation. Long-term potentiation-like plasticity and its reversibility were studied in the motor cortex of 10 healthy subjects, 10 patients with Parkinson's disease and levodopa-induced dyskinesias, who took half of the regular dose of levodopa and 10 patients with Parkinson's disease without levodopa-induced dyskinesias, who took either half or the full dose of levodopa. Patients with Parkinson's disease without levodopa-induced dyskinesias had normal long-term potentiation- and depotentiation-like effects when they took their full dose of levodopa, but there was no long-term potentiation-like effect when they were on half dose of levodopa. In contrast, patients with levodopa-induced dyskinesias could be successfully potentiated when they were on half their usual dose of levodopa; however, they were unresponsive to the depotentiation protocol. The results suggest that depotentiation is abnormal in the motor cortex of patients with Parkinson's disease with levodopa-induced dyskinesias and that their long-term potentiation-like plasticity is more readily affected by administration of levodopa than their clinical symptoms.

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