Document Detail


Electrophysiological and behavioral evidence that modulation of metabotropic glutamate receptor 4 with a new agonist reverses experimental parkinsonism.
MedLine Citation:
PMID:  19525404     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Developing nondopaminergic palliative treatments for Parkinson's disease represents a major challenge to avoid the debilitating side effects produced by L-DOPA therapy. Increasing interest is addressed to the selective targeting of group III metabotropic glutamate (mGlu) receptors that inhibit transmitter release at presumably overactive synapses in the basal ganglia. Here we characterize the functional action of a new orthosteric group III mGlu agonist, LSP1-2111, with a preferential affinity for mGlu4 receptor. In mouse brain slices, LSP1-2111 inhibits striatopallidal GABAergic transmission by selectively activating the mGlu4 receptor but has no effect at a synapse modulated solely by the mGlu7 and mGlu8 receptors. Intrapallidal LSP1-2111 infusion reverses the akinesia produced by nigrostriatal dopamine depletion in a reaction time task, whereas an mGlu8-receptor agonist has no effect. Finally, systemic administration of LSP1-2111 counteracts haloperidol-induced catalepsy, opening promising perspectives for the development of antiparkinsonian therapeutic strategies focused on orthosteric mGlu4-receptor agonists.
Authors:
Corinne Beurrier; Sebastien Lopez; Delphine Révy; Chelliah Selvam; Cyril Goudet; Morgane Lhérondel; Paolo Gubellini; Lydia Kerkerian-LeGoff; Francine Acher; Jean-Philippe Pin; Marianne Amalric
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-06-12
Journal Detail:
Title:  FASEB journal : official publication of the Federation of American Societies for Experimental Biology     Volume:  23     ISSN:  1530-6860     ISO Abbreviation:  FASEB J.     Publication Date:  2009 Oct 
Date Detail:
Created Date:  2009-10-02     Completed Date:  2009-11-05     Revised Date:  2012-02-15    
Medline Journal Info:
Nlm Unique ID:  8804484     Medline TA:  FASEB J     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3619-28     Citation Subset:  IM    
Affiliation:
Institut de Biologie du Développement de Marseille Luminy, UMR 6216 CNRS-Université de la Méditerranée, Marseille, France.
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MeSH Terms
Descriptor/Qualifier:
Aminobutyric Acids / therapeutic use*
Animals
Antiparkinson Agents / therapeutic use*
Behavior / drug effects
Catalepsy / chemically induced,  drug therapy
Cell Line
Disease Models, Animal
Electrophysiological Phenomena
Globus Pallidus / drug effects,  physiopathology
Haloperidol / pharmacology
Humans
Mice
Mice, Inbred C57BL
Parkinsonian Disorders / drug therapy*,  physiopathology*
Phosphinic Acids / therapeutic use*
Rats
Receptors, Metabotropic Glutamate / agonists*
Synaptic Transmission / drug effects
Chemical
Reg. No./Substance:
0/Aminobutyric Acids; 0/Antiparkinson Agents; 0/LSP1 2111; 0/Phosphinic Acids; 0/Receptors, Metabotropic Glutamate; 0/metabotropic glutamate receptor 4; 52-86-8/Haloperidol

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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