N-methyl-D-aspartate releases gamma-aminobutyric acid from rat striatum in vivo: a microdialysis study using a novel preloading method.
In vivo microdialysis was used in conjunction with a novel dual-label preloading method to monitor changes in extracellular levels of gamma-aminobutyric acid (GABA) and glutamate due to N-methyl-D-aspartate (NMDA) infusion in the striatum of conscious, unrestrained rats. [14C]GABA and [3H]glutamate were applied in the dialysis stream for a preloading period of 30 min, after which dialysis perfusion was continued for up to 6 h and dialysate samples were collected for analysis by liquid scintillation spectrometry. NMDA (300 microM in the dialysate) caused significant rises in both 14C and 3H content measured in the dialysates, the majority of which remained associated with the preloaded GABA and glutamate, respectively. The NMDA-evoked release of both GABA and glutamate was blocked by the specific NMDA receptor antagonist 3-[(+/-)-2-carboxypiperazin-4-yl]propyl-1-phosphonic acid (CPP), indicating that the response was receptor mediated. The NMDA-stimulated release of glutamate was also totally abolished by concomitant application of the adenosine agonist 2-chloroadenosine or by prior frontal decortication. However, these two treatments caused little change in NMDA-evoked GABA release. These results show that NMDA causes release of GABA from the striatum in vivo by an NMDA receptor-mediated mechanism and that the majority of this release is not secondary to glutamate release from terminals of the corticostriate pathway. In addition, they confirm the results of previous studies investigating the effect of NMDA on endogenous glutamate release.
Young
A M
AM
Department of Biochemistry, Imperial College of Science, Technology and Medicine, London, England.
Bradford
H F
HF
D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism; D002250:Carbon Radioisotopes; D002851:Chromatography, High Pressure Liquid; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D003956:Dialysis / Q000379:methods; D005971:Glutamates / Q000378:metabolism; D018698:Glutamic Acid; D005973:Glutamine / Q000378:metabolism; D007263:Infusions, Parenteral; D007700:Kinetics; D008297:Male; D016202:N-Methylaspartate / Q000008:administration & dosage / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D013997:Time Factors; D014316:Tritium; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D002250:Carbon Radioisotopes; D005971:Glutamates; D010879:Piperazines; D016194:Receptors, N-Methyl-D-Aspartate; D005973:Glutamine; D014316:Tritium; D001224:Aspartic Acid; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D016202:N-Methylaspartate; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid