ParkinsonFranceV1, Main, Merge, bibRecord, 003147

Functional interaction between mGlu 5 and NMDA receptors in a rat model of Parkinson's disease

Identifieur interne : 003147 ( Main/Merge ); précédent : 003146; suivant : 003148

Functional interaction between mGlu 5 and NMDA receptors in a rat model of Parkinson's disease

Auteurs : Nathalie Turle-Lorenzo [France] ; Nathalie Breysse [France] ; Christelle Baunez [France] ; Marianne Amalric [France]

Source :

Psychopharmacologia [ 0033-3158 ] ; 2005.

RBID : Pascal:05-0297430

Descripteurs français

Pascal (Inist)
- Interaction, Récepteur NMDA, Modèle animal, Rat, Parkinson maladie, Noyau gris central, Pyridine, Dizocilpine, Antagoniste, Oxidopamine, Lésion, Temps réaction, Akinésie, Glutamate, Animal, Récepteur métabotropique, Neuroprotecteur.

English descriptors

KwdEn :
- Akinesia, Animal, Animal model, Antagonist, Basal ganglion, Dizocilpine, Glutamate, Interaction, Lesion, Metabotropic receptor, NMDA receptor, Neuroprotective agent, Oxidopamine, Parkinson disease, Pyridine, Rat, Reaction time.

Abstract

Rationale: Electrophysiological evidence suggests a synergistic relationship between metabotropic (mGlu) and ionotropic (iGlu) glutamate receptors. The functional consequences of these interactions have not been investigated in neurodegenerative diseases such as in Parkinson's disease. Objective: The goals ofthis study are as follows: (1) to investigate the effects of 2-methyl-6-(phenylethynyl)-pyridine (MPEP) and dizocilpine (MK- 801), antagonists at metabotropic glutamate 5 (mGlu5) and NMDA receptors, respectively, on the akinetic syndrome observed in bilateral 6-OHDA-lesioned rats; (2) to investigate if the effects of MPEP were potentiated by co-treatment with a behaviorally inactive dose of MK-801; and (3) to investigate the effects of L-DOPA alone and in combination with MPEP on the akinetic syndrome observed in 6-OHDA-lesioned rats. Methods: The effects of the different treatments (single and co-treatment) administered for 3 weeks were measured in 6-OHDA-lesioned rats trained to release a lever rapidly after a visual stimulus onset in a simple reaction time task. Results: MPEP 0.75 mg/kg reversed the akinetic deficits produced by striatal dopamine depletion, while MPEP 0.375 mg/kg had no effect. Co-administration with MK-801 0.02 mg/kg, ineffective alone, failed to speed the recovery process of MPEP 0.75 mg/kg but revealed the anti-akinetic action of MPEP 0.375 mg/kg. L-DOPA 3 mg/kg alone had a potent anti-akinetic effect in 6-OHDA lesioned rats, and this effect was not potentiated by a subthreshold MPEP treatment. Conclusion: These results support a critical role for mGlu5 receptor blockade in improving parkinsonian symptomatology either as a single treatment or in combination with low concentrations of L-DOPA and demonstrate an interaction between NMDA and mGluR5 in regulating these effects.

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Le document en format XML

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<front><div type="abstract" xml:lang="en">Rationale: Electrophysiological evidence suggests a synergistic relationship between metabotropic (mGlu) and ionotropic (iGlu) glutamate receptors. The functional consequences of these interactions have not been investigated in neurodegenerative diseases such as in Parkinson's disease. Objective: The goals ofthis study are as follows: (1) to investigate the effects of 2-methyl-6-(phenylethynyl)-pyridine (MPEP) and dizocilpine (MK- 801), antagonists at metabotropic glutamate 5 (mGlu5) and NMDA receptors, respectively, on the akinetic syndrome observed in bilateral 6-OHDA-lesioned rats; (2) to investigate if the effects of MPEP were potentiated by co-treatment with a behaviorally inactive dose of MK-801; and (3) to investigate the effects of L-DOPA alone and in combination with MPEP on the akinetic syndrome observed in 6-OHDA-lesioned rats. Methods: The effects of the different treatments (single and co-treatment) administered for 3 weeks were measured in 6-OHDA-lesioned rats trained to release a lever rapidly after a visual stimulus onset in a simple reaction time task. Results: MPEP 0.75 mg/kg reversed the akinetic deficits produced by striatal dopamine depletion, while MPEP 0.375 mg/kg had no effect. Co-administration with MK-801 0.02 mg/kg, ineffective alone, failed to speed the recovery process of MPEP 0.75 mg/kg but revealed the anti-akinetic action of MPEP 0.375 mg/kg. L-DOPA 3 mg/kg alone had a potent anti-akinetic effect in 6-OHDA lesioned rats, and this effect was not potentiated by a subthreshold MPEP treatment. Conclusion: These results support a critical role for mGlu5 receptor blockade in improving parkinsonian symptomatology either as a single treatment or in combination with low concentrations of L-DOPA and demonstrate an interaction between NMDA and mGluR5 in regulating these effects.</div>
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	La maladie de Parkinson en France (serveur d'exploration)
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La maladie de Parkinson en France (serveur d'exploration)

Functional interaction between mGlu 5 and NMDA receptors in a rat model of Parkinson's disease

Functional interaction between mGlu 5 and NMDA receptors in a rat model of Parkinson's disease

Source :

Descripteurs français

English descriptors

Abstract

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