Format

Send to

Choose Destination
Nat Neurosci. 2003 May;6(5):501-6.

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

Author information

1
Clinica Neurologica, Dipartimento di Neuroscienze, Università di Roma Tor Vergata, Via Montpellier 1, 00133 Rome, Italy.

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.

Comment in

PMID:
12665799
DOI:
10.1038/nn1040
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Nature Publishing Group
Loading ...
Support Center