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      Loss of bidirectional striatal synaptic plasticity in L-DOPA-induced dyskinesia.

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          Abstract

          Long-term treatment with the dopamine precursor levodopa (L-DOPA) induces dyskinesia in Parkinson's disease (PD) patients. We divided hemiparkinsonian rats treated chronically with L-DOPA into two groups: one showed motor improvement without dyskinesia, and the other developed debilitating dyskinesias in response to the treatment. We then compared the plasticity of corticostriatal synapses between the two groups. High-frequency stimulation of cortical afferents induced long-term potentiation (LTP) of corticostriatal synapses in both groups of animals. Control and non-dyskinetic rats showed synaptic depotentiation in response to subsequent low-frequency synaptic stimulation, but dyskinetic rats did not. The depotentiation seen in both L-DOPA-treated non-dyskinetic rats and intact controls was prevented by activation of the D1 subclass of dopamine receptors or inhibition of protein phosphatases. The striata of dyskinetic rats contained abnormally high levels of phospho[Thr34]-DARPP-32, an inhibitor of protein phosphatase 1. These results indicate that abnormal information storage in corticostriatal synapses is linked with the development of L-DOPA-induced dyskinesia.

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          Author and article information

          Journal
          Nat Neurosci
          Nature neuroscience
          Springer Science and Business Media LLC
          1097-6256
          1097-6256
          May 2003
          : 6
          : 5
          Affiliations
          [1 ] Clinica Neurologica, Dipartimento di Neuroscienze, Università di Roma Tor Vergata, Via Montpellier 1, 00133 Rome, Italy.
          Article
          nn1040
          10.1038/nn1040
          12665799
          f3a97848-7c20-47b8-b4f7-3b40f51cdd6f
          History

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