Glutamate and aspartate do not exhibit the same changes in their extracellular concentrations in the rat striatum after N-methyl-D-aspartate local administration.
To determine whether glutamate (Glu) and aspartate (Asp) undergo a similar regulation of their extracellular levels, Glu and Asp were simultaneously monitored in the striatum of anesthetized rats after local N-methyl-D-aspartate (NMDA) receptor stimulation, using 1-min in vivo microdialysis coupled to capillary electrophoresis with laser-induced fluorescence detection. Application of NMDA (10 min, 10(-3) M) through the dialysis probe induced 1) an increase (+50%) in Asp during the NMDA administration and 2) a surprising biphasic effect on Glu, with a rapid increase (+30%) and a return to baseline before the end of NMDA application, followed by a second increase (+40%) occurring after and linked to the end of NMDA administration. When studied in the presence of 10 microM tetrodotoxin (TTX) or 0.1 mM Ca(2+), the increase in Asp was partially TTX-dependent, and the early increase in Glu appeared to be partially TTX and Ca(2+) dependent, whereas the second increase in Glu was not. The second increase in Glu level was still present when NMDA antagonists (AP5 or MK-801) were administered at the end of NMDA application. Finally, only extracellular Asp was increased through application of lower NMDA concentrations (10(-4) M, 10(-5) M), whereas extracellular Glu was not affected. In conclusion, these results suggest a differential control of Glu and Asp extracellular levels in rat striatum by distinct mechanisms linked to NMDA receptors and involving neuronal or nonneuronal release.
Parrot
Sandrine
S
Laboratoire de Neuropharmacologie et Neurochimie, INSERM U512, Faculté de Pharmacie, Université Claude Bernard, Lyon, France. sparrot@rockefeller.univ-lyon1.fr
Bert
Lionel
L
Renaud
Bernard
B
Denoroy
Luc
L
D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism*; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D005110:Extracellular Space / Q000187:drug effects* / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism*; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists / Q000378:metabolism
D016194:Receptors, N-Methyl-D-Aspartate; D001224:Aspartic Acid; D018698:Glutamic Acid; D016202:N-Methylaspartate