title: NR2A and NR2B subunit containing NMDA receptors differentially regulate striatal output pathways.
abstract: Triple probe microdialysis was employed to investigate whether striatal NR2A and NR2B subunit containing NMDA receptors regulate the activity of striato-pallidal and striato-nigral projection neurons. Probes were implanted in the striatum, ipsilateral globus pallidus and substantia nigra reticulata. Intrastriatal perfusion with the NR2A subunit selective antagonist (R)-[(S)-1-(4-bromo-phenyl)-ethylamino]-(2,3-dioxo-1,2,3,4-tetrahydroquinoxalin-5-yl)-methyl]-phosphonic acid (NVP-AAM077) reduced pallidal GABA and increased nigral glutamate (GLU) release whereas perfusion with the NR2B subunit selective antagonist (R-(R*,S*)-alpha-(4-hydroxyphenyl)-beta-methyl-4-(phenylmethyl)-1-piperidinepropanol (Ro 25-6981) reduced nigral GABA and elevated striatal and pallidal GLU release. To confirm that changes in GABA levels were because of blockade of (GLUergic-driven) tonic activity of striatofugal neurons, tetrodotoxin was perfused in the striatum. Tetrodotoxin reduced both pallidal and nigral GABA release without changing GLU levels. To investigate whether striatal NR2A and NR2B subunits were also involved in phasic activation of striatofugal neurons, NVP-AAM077 and Ro 25-6981 were challenged against a NMDA concentration able to evoke GABA release in the three areas. Both antagonists prevented the NMDA-induced striatal GABA release. NVP-AAM077 also prevented the NMDA-induced surge in GABA release in the globus pallidus, whereas Ro 25-6981 attenuated it in the substantia nigra. We conclude that striatal NMDA receptors containing NR2A and NR2B subunits preferentially regulate the striato-pallidal and striato-nigral projection neurons, respectively.
authors.affiliation: Department of Experimental and Clinical Medicine, Section of Pharmacology, and Istituto Nazionale di Neuroscience, University of Ferrara, Ferrara, Italy.
authors.forename: Martina
authors.initials: M
authors.lastname: Fantin
authors.forename: Matteo
authors.initials: M
authors.lastname: Marti
authors.forename: Yves P
authors.initials: YP
authors.lastname: Auberson
authors.forename: Michele
authors.initials: M
authors.lastname: Morari
mesh_terms: D000818:Animals; D004525:Efferent Pathways / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D045604:Extracellular Fluid / Q000187:drug effects / Q000378:metabolism; D018755:GABA Agonists / Q000494:pharmacology; D005917:Globus Pallidus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism*; D008297:Male; D017551:Microdialysis; D017072:Neostriatum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism*; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013378:Substantia Nigra / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D018691:Excitatory Amino Acid Antagonists; D018755:GABA Agonists; C120997:NR2A NMDA receptor; C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; D026941:Sodium Channel Blockers; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid