Antiparkinsonian action of a selective group III mGlu receptor agonist is associated with reversal of subthalamonigral overactivity
Activation of group III metabotropic glutamate (mGlu) receptors has been recently highlighted as a potential approach in the treatment of Parkinson's disease (PD). This study evaluates the antiparkinsonian action of systemic administration of the broad-spectrum agonist of group III mGlu recepto...
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| Format: | Article |
| Language: | English |
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Elsevier
2012-04-01
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| Series: | Neurobiology of Disease |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996111004311 |
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| author | S. Lopez L. Jouve N. Turle-Lorenzo L. Kerkerian-LeGoff P. Salin M. Amalric |
| author_facet | S. Lopez L. Jouve N. Turle-Lorenzo L. Kerkerian-LeGoff P. Salin M. Amalric |
| author_sort | S. Lopez |
| collection | DOAJ |
| description | Activation of group III metabotropic glutamate (mGlu) receptors has been recently highlighted as a potential approach in the treatment of Parkinson's disease (PD). This study evaluates the antiparkinsonian action of systemic administration of the broad-spectrum agonist of group III mGlu receptors, 1-aminocyclopentane-1,3,4-tricarboxylic acid (ACPT-I), and investigates its site of action within the basal ganglia circuitry. Acute injection of ACPT-I reverses haloperidol-induced catalepsy, an index of akinesia in rodents. In a rat model of early PD based on partial bilateral nigrostriatal lesions, chronic (2 weeks) administration of ACPT-I is required to efficiently alleviate the akinetic deficit evidenced in a reaction time task. This treatment counteracts the post-lesional increases in the gene expression of cytochrome oxidase subunit I, a metabolic marker of neuronal activity, in the overall subthalamic nucleus and in the lateral motor part of the substantia nigra pars reticulata (SNr) but has no effect in the globus pallidus. Paradoxically, ACPT-I administration in sham animals impairs performance and induces overexpression of cytochrome oxidase subunit I mRNA in the lateral SNr, and has no effect in the subthalamic nucleus or globus pallidus.Altogether, our results provide new evidence for the antiparkinsonian efficiency of group III mGlu receptor agonism, point to the regulation of the overactive subthalamo-nigral connection as a main site of action in an early stage of PD and underline the complex interplay between these receptors and the dopaminergic system to regulate basal ganglia function in control and PD conditions. |
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| format | Article |
| id | doaj.art-72234239eea74c3db9f8c4ef3f320869 |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-12-17T23:58:46Z |
| publishDate | 2012-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-72234239eea74c3db9f8c4ef3f3208692022-12-21T21:28:00ZengElsevierNeurobiology of Disease1095-953X2012-04-014616977Antiparkinsonian action of a selective group III mGlu receptor agonist is associated with reversal of subthalamonigral overactivityS. Lopez0L. Jouve1N. Turle-Lorenzo2L. Kerkerian-LeGoff3P. Salin4M. Amalric5Aix-Marseille Univ, Laboratoire de Neurobiologie de la Cognition, 13331 Marseille Cx 3, France; CNRS UMR7291, Laboratoire de Neurosciences Cognitives, 13331 Marseille Cx 3, FranceAix-Marseille Univ, IBDML, Institut de Biologie du Développement de Marseille Luminy, 13288 Marseille Cx 9, France; CNRS UMR 7288, Institut de Biologie du Développement de Marseille Luminy, 13288 Marseille Cx 9, FranceAix-Marseille Univ, Laboratoire de Neurobiologie de la Cognition, 13331 Marseille Cx 3, France; CNRS UMR7291, Laboratoire de Neurosciences Cognitives, 13331 Marseille Cx 3, FranceAix-Marseille Univ, IBDML, Institut de Biologie du Développement de Marseille Luminy, 13288 Marseille Cx 9, France; CNRS UMR 7288, Institut de Biologie du Développement de Marseille Luminy, 13288 Marseille Cx 9, FranceAix-Marseille Univ, IBDML, Institut de Biologie du Développement de Marseille Luminy, 13288 Marseille Cx 9, France; CNRS UMR 7288, Institut de Biologie du Développement de Marseille Luminy, 13288 Marseille Cx 9, FranceAix-Marseille Univ, Laboratoire de Neurobiologie de la Cognition, 13331 Marseille Cx 3, France; CNRS UMR7291, Laboratoire de Neurosciences Cognitives, 13331 Marseille Cx 3, France; Corresponding author at: Aix-Marseille Univ, Laboratoire de Neurosciences Cognitives, Case C, 3 Place Victor Hugo, 13331 Marseille Cx 3, France. Fax: +33 4 88 57 68 72.Activation of group III metabotropic glutamate (mGlu) receptors has been recently highlighted as a potential approach in the treatment of Parkinson's disease (PD). This study evaluates the antiparkinsonian action of systemic administration of the broad-spectrum agonist of group III mGlu receptors, 1-aminocyclopentane-1,3,4-tricarboxylic acid (ACPT-I), and investigates its site of action within the basal ganglia circuitry. Acute injection of ACPT-I reverses haloperidol-induced catalepsy, an index of akinesia in rodents. In a rat model of early PD based on partial bilateral nigrostriatal lesions, chronic (2 weeks) administration of ACPT-I is required to efficiently alleviate the akinetic deficit evidenced in a reaction time task. This treatment counteracts the post-lesional increases in the gene expression of cytochrome oxidase subunit I, a metabolic marker of neuronal activity, in the overall subthalamic nucleus and in the lateral motor part of the substantia nigra pars reticulata (SNr) but has no effect in the globus pallidus. Paradoxically, ACPT-I administration in sham animals impairs performance and induces overexpression of cytochrome oxidase subunit I mRNA in the lateral SNr, and has no effect in the subthalamic nucleus or globus pallidus.Altogether, our results provide new evidence for the antiparkinsonian efficiency of group III mGlu receptor agonism, point to the regulation of the overactive subthalamo-nigral connection as a main site of action in an early stage of PD and underline the complex interplay between these receptors and the dopaminergic system to regulate basal ganglia function in control and PD conditions.http://www.sciencedirect.com/science/article/pii/S0969996111004311Basal ganglia6-Hydroxydopamine (6-OHDA)GlutamateReaction time taskIn situ hybridizationRat |
| spellingShingle | S. Lopez L. Jouve N. Turle-Lorenzo L. Kerkerian-LeGoff P. Salin M. Amalric Antiparkinsonian action of a selective group III mGlu receptor agonist is associated with reversal of subthalamonigral overactivity Neurobiology of Disease Basal ganglia 6-Hydroxydopamine (6-OHDA) Glutamate Reaction time task In situ hybridization Rat |
| title | Antiparkinsonian action of a selective group III mGlu receptor agonist is associated with reversal of subthalamonigral overactivity |
| title_full | Antiparkinsonian action of a selective group III mGlu receptor agonist is associated with reversal of subthalamonigral overactivity |
| title_fullStr | Antiparkinsonian action of a selective group III mGlu receptor agonist is associated with reversal of subthalamonigral overactivity |
| title_full_unstemmed | Antiparkinsonian action of a selective group III mGlu receptor agonist is associated with reversal of subthalamonigral overactivity |
| title_short | Antiparkinsonian action of a selective group III mGlu receptor agonist is associated with reversal of subthalamonigral overactivity |
| title_sort | antiparkinsonian action of a selective group iii mglu receptor agonist is associated with reversal of subthalamonigral overactivity |
| topic | Basal ganglia 6-Hydroxydopamine (6-OHDA) Glutamate Reaction time task In situ hybridization Rat |
| url | http://www.sciencedirect.com/science/article/pii/S0969996111004311 |
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