Blockade of mGluR glutamate receptors in the subthalamic nucleus ameliorates motor asymmetry in an animal model of Parkinson's disease.

TitleBlockade of mGluR glutamate receptors in the subthalamic nucleus ameliorates motor asymmetry in an animal model of Parkinson's disease.
Publication TypeJournal Article
Year of Publication2006
AuthorsPhillips, JM, Lam HA, Ackerson LC, Maidment NT
JournalThe European journal of neuroscience
Volume23
Issue1
Pagination151-60
Date Published2006 Jan
ISSN0953-816X
KeywordsAnimals, Behavior, Animal, Disease Models, Animal, Dopamine, Dose-Response Relationship, Drug, Drug Interactions, Excitatory Amino Acid Antagonists, Functional Laterality, Male, Motor Activity, Oxidopamine, Parkinson Disease, Parkinson Disease, Secondary, Pyridines, Rats, Rats, Sprague-Dawley, Receptors, Metabotropic Glutamate, Subthalamic Nucleus, Sympatholytics, Time Factors
Abstract

It has been suggested that Group I metabotropic glutamate receptor antagonists could have potential therapeutic value in the treatment of Parkinson's disease. There is evidence that when given systemically, 2-methyl-6-(phenylethynyl)-pyridine (MPEP), a metabotropic glutamate receptor type 5 (mGluR5) antagonist, produces anti-parkinsonian effects in animal models, but the site of action has not been directly established. In the present study, we examined whether the subthalamic nucleus (STN) and its output structures may mediate such an effect using a unilateral rat model of Parkinson's disease. A battery of simple behavioral tests, reliably sensitive to dopamine depletion, was applied consecutively: (i) prior to surgery; (ii) 3 weeks following a unilateral 6-hydroxydopamine lesion of the substantia nigra pars compacta; (iii) at 1 h, 24 h and 4 days following a microinjection of MPEP, via an indwelling cannula, into the STN, entopeduncular nucleus (EP) or substantia nigra zona reticulata. Unilaterally dopamine-depleted animals typically had severe motor and sensorimotor asymmetries 3 weeks following surgery. Microinjection of 25 nmol MPEP into the STN of these animals significantly attenuated these asymmetries relative to vehicle. Further microinjections of lower doses (5 and 10 nmol) revealed a dose-response effect. Microinjection of MPEP into either the EP or substantia nigra zona reticulata was without effect. These data suggest that MPEP may act at the level of the STN to reduce glutamatergic overactivity and thereby induce anti-parkinsonian effects.

DOI10.1111/j.1553-2712.2011.01024.x
Alternate JournalEur. J. Neurosci.