US EPA

2317582 

Journal Article 

GluN2A and GluN2B NMDA receptor subunits differentially modulate striatal output pathways and contribute to levodopa-induced abnormal involuntary movements in dyskinetic rats 

Mabrouk, OS; Mela, F; Calcagno, M; Budri, M; Viaro, R; Dekundy, A; Parsons, CG; Auberson, YP; Morari, M 

2013 

Yes 

ACS Chemical Neuroscience
ISSN: 1948-7193 

AMER CHEMICAL SOC 

WASHINGTON 

4 

5 

808-816 

English 

23611155 

10.1021/cn400016d 

WOS:000319250400018 

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.