Mabrouk, OS, Mela, F, Calcagno, M, Budri, M, Viaro, R, Dekundy, A, Parsons, CG, Auberson, YP and Morari, M (2013) GluN2A and GluN2B NMDA receptor subunits differentially modulate striatal output pathways and contribute to levodopa-induced abnormal involuntary movements in dyskinetic rats. ACS Chemical Neuroscience. pp. 808-816.

Abstract

Dual probe microdialysis was used to investigate whether GluN2A and GluN2B NMDA receptor subunits regulate striatal output pathways under dyskinetic conditions. The preferential GluN2A antagonist NVP-AAM077 perfused in the dopamine-depleted striatum of 6-hydroxydopamine hemilesioned dyskinetic rats reduced GABA and glutamate levels in globus pallidus whereas the selective GluN2B antagonist Ro 25-6981 elevated glutamate without affecting pallidal GABA. Moreover, intrastriatal NVP-AAM077 did not affect GABA but elevated glutamate levels in substantia nigra reticulata whereas Ro 25-6981 elevated GABA and reduced nigral glutamate. To investigate whether GluN2A and GluN2B NMDA receptor subunits are involved in motor pathways underlying dyskinesia expression, systemic NVP-AAM077 and Ro 25-6981 were tested for their ability to attenuate levodopa-induced abnormal involuntary movements. NVP-AAM077 failed to prevent dyskinesia while Ro 25-6981 mildly attenuated it. We conclude that in the dyskinetic striatum, striatal GluN2A subunits tonically stimulate the striato-pallidal pathway whereas striatal GluN2B subunits tonically inhibit striato-nigral projections. Moreover, GluN2A subunits are not involved in dyskinesia expression whereas GluN2B subunits minimally contribute to it. 2013 American Chemical Society

Item Type:	Article
Additional Information:	pubid: 106 nvp_institute: NIBR contributor_address: (Mabrouk, Mela, Calcagno, Budri, Morari) Department of Medical Sciences, Section of Pharmacology, University of Ferrara, via Fossato di Mortara 17-19, 44121 FERRARA, Italy (Mabrouk, Mela, Calcagno, Budri, Morari) National Institute of Neuroscience, Ferrara, Italy (Mela, Dekundy, Parsons) Merz Pharmaceuticals, Frankfurt am Main, Germany (Viaro) Department of Biomedical and Specialty Surgical Sciences, Section of Human Physiology, University of Ferrara, Ferrara, Italy (Viaro) Department of Robotics, Brain and Cognitive Sciences, Istituto Italiano di Tecnologia, Genova, Italy (Auberson) Novartis Institutes for BioMedical Research, Basel, Switzerland
Date Deposited:	13 Oct 2015 13:13
Last Modified:	13 Oct 2015 13:13
URI:	https://oak.novartis.com/id/eprint/21944