کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
3069486 1580684 2012 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Antiparkinsonian action of a selective group III mGlu receptor agonist is associated with reversal of subthalamonigral overactivity
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی عصب شناسی
پیش نمایش صفحه اول مقاله
Antiparkinsonian action of a selective group III mGlu receptor agonist is associated with reversal of subthalamonigral overactivity
چکیده انگلیسی

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.


► In parkinsonian models, group III mGluR agonist systemic action is poorly understood.
► Group III mGluR agonist ACPT-I treatment reduces akinesia in 6-OHDA lesioned rats.
► In lesioned animals, ACPT-I treatment normalizes STN and SNr overactivity.
► In control rats, ACPT-I induces motor deficits and increases activity in the SNr.
► STN is a critical site of action of ACPT-I to relieve parkinsonian symptoms.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neurobiology of Disease - Volume 46, Issue 1, April 2012, Pages 69–77
نویسندگان
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