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Metabotropic glutamate receptor subtype 4 selectively modulates both glutamate and GABA transmission in the striatum: implications for Parkinson’s disease treatment
Author(s) -
Cuomo Dario,
Martella Giuseppina,
Barabino Emanuela,
Platania Paola,
Vita Daniela,
Madeo Graziella,
Selvam Chelliah,
Goudet Cyril,
Oueslati Nadia,
Pin JeanPhilippe,
Acher Francine,
Pisani Antonio,
Beurrier Corinne,
Melon Christophe,
KerkerianLe Goff Lydia,
Gubellini Paolo
Publication year - 2009
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2009.06036.x
Subject(s) - metabotropic glutamate receptor , glutamate receptor , neurotransmission , neuroscience , striatum , metabotropic receptor , metabotropic glutamate receptor 5 , metabotropic glutamate receptor 6 , metabotropic glutamate receptor 1 , basal ganglia , inhibitory postsynaptic potential , chemistry , biology , pharmacology , receptor , biochemistry , central nervous system , dopamine
Alterations of striatal synaptic transmission have been associated with several motor disorders involving the basal ganglia, such as Parkinson’s disease. For this reason, we investigated the role of group‐III metabotropic glutamate (mGlu) receptors in regulating synaptic transmission in the striatum by electrophysiological recordings and by using our novel orthosteric agonist (3 S )‐3‐[(3‐amino‐3‐carboxypropyl(hydroxy)phosphinyl)‐hydroxymethyl]‐5‐nitrothiophene (LSP1‐3081) and l ‐2‐amino‐4‐phosphonobutanoate (L‐AP4). Here, we show that both drugs dose‐dependently reduced glutamate‐ and GABA‐mediated post‐synaptic potentials, and increased the paired‐pulse ratio. Moreover, they decreased the frequency, but not the amplitude, of glutamate and GABA spontaneous and miniature post‐synaptic currents. Their inhibitory effect was abolished by ( RS )‐α‐cyclopropyl‐4‐phosphonophenylglycine and was lost in slices from mGlu4 knock‐out mice. Furthermore, ( S )‐3,4‐dicarboxyphenylglycine did not affect glutamate and GABA transmission. Finally, intrastriatal LSP1‐3081 or L‐AP4 injection improved akinesia measured by the cylinder test. These results demonstrate that mGlu4 receptor selectively modulates striatal glutamate and GABA synaptic transmission, suggesting that it could represent an interesting target for selective pharmacological intervention in movement disorders involving basal ganglia circuitry.