Activation of metabotropic glutamate 4 receptors decreases L-DOPA-induced dyskinesia in a mouse model of Parkinson's disease

• Published in: Journal of Parkinson's disease Vol. 1; no. 4; p. 339
• Main Authors: Lopez, Sébastien, Bonito-Oliva, Alessandra, Pallottino, Simone, Acher, Francine, Fisone, Gilberto
• Format: Journal Article
• Language: English
• Published: Netherlands 2011
• Subjects: Adrenergic Agents - toxicity; Aminobutyrates - pharmacology; Aminobutyrates - therapeutic use; Animals; Antiparkinson Agents - adverse effects; Benserazide - therapeutic use; Corpus Striatum - drug effects; Corpus Striatum - metabolism; Disease Models, Animal; Dyskinesia, Drug-Induced - drug therapy; Dyskinesia, Drug-Induced - metabolism; Excitatory Amino Acid Agonists - pharmacology; Excitatory Amino Acid Agonists - therapeutic use; Gene Expression Regulation - drug effects; Levodopa - adverse effects; Male; Mice; Mice, Inbred C57BL; Oxidopamine - toxicity; Parkinson Disease - drug therapy; Parkinson Disease - etiology; Phosphinic Acids - pharmacology; Phosphinic Acids - therapeutic use; Receptors, Metabotropic Glutamate - metabolism; Time Factors
• ISSN: 1877-718X
• DOI: 10.3233/JPD-2011-11066

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.