Activation of metabotropic glutamate 4 receptors decreases L-DOPA-induced dyskinesia in a mouse model of Parkinson's disease.
J Parkinsons Dis
; 1(4): 339-46, 2011.
Article
em En
| MEDLINE
| ID: mdl-23939343
ABSTRACT
Group III metabotropic glutamate (mGlu) receptors modulate glutamatergic and GABAergic transmission in the basal ganglia. In this study, we examined a novel orthosteric agonist at the mGlu4 receptor, LSP1-2111, for its ability to affect L-DOPA-induced dyskinesia (LID), in a mouse model. In 6-OHDA-lesioned mice treated with L-DOPA, chronic co-administration of LSP1-2111 significantly attenuated the development of abnormal involuntary movements, which are regarded as a marker of dyskinesia. In contrast, a single injection of LSP1-2111 did not modify the expression of LID, once this condition had been established by previous administration of L-DOPA. LSP1-2111 did not affect L-DOPA-induced cAMP and extracellular signal-regulated protein kinase signaling, which have been previoulsy implicated in dyskinesia. These results indicate that co-administration of LSP1-2111 may improve the efficacy of standard L-DOPA therapy by attenuating its liability for dyskinesia.
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Base de dados:
MEDLINE
Assunto principal:
Levodopa
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Regulação da Expressão Gênica
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Receptores de Glutamato Metabotrópico
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Discinesia Induzida por Medicamentos
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Antiparkinsonianos
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article