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Effects of Ionotropic Excitatory Amino Acid Receptor Antagonists on Glutamate Transport and Transport‐Mediated Changes in Extracellular Excitatory Amino Acids in the Rat Striatum
Author(s) -
Bloc Alain,
Samuel Denise,
Forni Claude,
Dusticier Nicole,
KerkerianLe Goff Lydia
Publication year - 1995
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1995.64041598.x
Subject(s) - dnqx , kainate receptor , nmda receptor , ionotropic effect , glutamate receptor , ampa receptor , biology , excitatory postsynaptic potential , metabotropic glutamate receptor 5 , neurotransmission , excitatory amino acid antagonists , 2 amino 5 phosphonovalerate , biochemistry , pharmacology , chemistry , metabotropic glutamate receptor , receptor
This study examined the effects of intrastriatal administration of ionotropic excitatory amino acid receptor antagonists on biochemical markers of excitatory amino acid transmission in the rat striatum. High‐affinity glutamate uptake was measured ex vivo on striatal homogenates 15 min after the local administration of either 6,7‐dinitroquinoxaline‐2,3‐dione (DNQX), a non‐NMDA receptor antagonist, or dl ‐2‐amino‐5‐phosphonopentanoic acid (AP5), a competitive NMDA antagonist, at various doses (10–500 pmol injected). DNQX induced a dose‐dependent increase in glutamate uptake rate, related to an increase in the V max of the transport process, whereas no significant change in glutamate uptake was detected after AP5 administration. Similar results were obtained from animals subjected to excitotoxic lesion of striatal neurons by kainate administration 15 days before the injection of DNQX or AP5. In a parallel series of experiments using in vivo microdialysis we showed that DNQX (10 −5 M ) in the dialysis probe diminished by ∼30–40% the increases in the concentrations of glutamate and aspartate elicited by l ‐ trans ‐pyrrolidine‐2,4‐dicarboxylic acid (1 m M ). These data suggest that presynaptic glutamate transmission in the rat striatum may undergo facilitatory autoregulatory processes involving ionotropic non‐NMDA receptors and highlight the view that transporters for glutamate may be potent regulatory sites for glutamatergic transmission.