title: Glutamate receptor regulation of rat nucleus accumbens neurons in vivo.
abstract: Extracellular single cell recording and microiontophoretic techniques were used to characterize the roles of ionotropic and metabotropic glutamate receptors (iGluRs and mGluRs) in glutamate-induced excitation of rat nucleus accumbens (NAc) neurons in vivo. Pulse-ejected glutamate (16-128 nA) induced a current-dependent increase in the firing of quiescent NAc neurons. A stronger excitatory response to alpha-amino-3-hydroxy-5-methyl-4-isoxazole-proprionic acid (AMPA) was observed at much lower ejection currents (0.1-6.4 nA). Compared to AMPA and glutamate, N-methyl-D-aspartate (NMDA) induced a much less potent excitation in a narrow current range (1-4 nA) and only when neurons were previously "primed" with other excitatory amino acids (EAAs). Higher ejection currents of all three EAA agonists drove NAc neurons into a state of apparent depolarization block. AMPA-evoked firing was selectively blocked by the AMPA receptor antagonist 6,7-dinitroquinoxaline-2,3-dione (DNQX) whereas NMDA-induced activity was selectively prevented by the NMDA receptor antagonist 2-amino-5-phosphonovalerate (D-AP5). DNQX, but not D-AP5, significantly attenuated glutamate-evoked activity. The mGluR receptor agonist (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-t-ACPD) failed to evoke activity of NAc neurons, but significantly reduced the excitatory effects of other EAAs. This modulatory effect of 1S,3R-t-ACPD was consistently blocked by the selective mGluR antagonist L(+)-2-amino-3-phopsonopropionic acid (L-AP3) whereas another mGluR antagonist (RS)-4-carboxy-3-hydroxy phenylglycine (4C3HPG) was inconsistent in this regard. These results indicate that the excitatory effects of glutamate on rat NAc neurons in vivo are primarily mediated by non-NMDA iGluRs and that mGluRs function to dampen excessive glutamate transmission through iGluRs.
authors.affiliation: Department of Neuroscience, University of Health Sciences, Chicago Medical School, Illinois 60064, USA.
authors.forename: X T
authors.initials: XT
authors.lastname: Hu
authors.forename: F J
authors.initials: FJ
authors.lastname: White
mesh_terms: D000818:Animals; D004594:Electrophysiology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000008:administration & dosage / Q000494:pharmacology; D066298:In Vitro Techniques; D007478:Iontophoresis; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000378:metabolism*; D009714:Nucleus Accumbens / Q000033:anatomy & histology / Q000166:cytology / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017470:Receptors, Glutamate / Q000378:metabolism*; D018094:Receptors, Metabotropic Glutamate / Q000187:drug effects / Q000502:physiology; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
chemical_list: D018690:Excitatory Amino Acid Agonists; D011810:Quinoxalines; D017470:Receptors, Glutamate; D018094:Receptors, Metabotropic Glutamate; D018698:Glutamic Acid; C056723:FG 9041; D016202:N-Methylaspartate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid