N‐Methyl‐d‐Aspartate Releases γ‐Aminobutyric Acid from Rat Striatum In Vivo: A Microdialysis Study Using a Novel Preloading Method

Abstract

In vivo microdialysis was used in conjunction with a novel dual-label preloading method to monitor changes in extracellular levels of y-aminobutyric acid (GABA) and glutamate due to N-methyl-D-aspartate (NMDA) infusion in the striaturn of conscious, unrestrained rats.[I4C]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 pLM in the dialysate) caused significant rises in both 14C and 'H 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. Key Words: y-Aminobutyric acid-Glutamate-Microdialysis--N-Methyl-D-aspartate-Preloading in vivo-Striatum. Young A. M. J. and Bradford H. F. NMethybaspartate releases y-aminobutyric acid from rat striatum in vivo: A microdialysis study using a novel preloading method.

Endogenous Glutamate Increases Extracellular Concentrations of Dopamine, GABA, and Taurine Through NMDA and AMPA/Kainate Receptors in Striatum of the Freely Moving Rat: A Microdialysis Study

“…In striatum, local infusion of the Glu agonist N-methyl-D-aspartate (NMDA) increases extracellular DA (Keefe et al, 1992;Moran et al, 1993;Kendrick et al, 1996), GABA (Moran et al, 1993;Young and Bradford, 1993;Kendrick et al, 1996), and Tau (Shibanoki et al, 1993). Also, intrastriatal infusion of cr-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA)/kainate-receptor agonists increases extracellular DA (Keefe et al, 1993;Kendrick et al, 1996;Smolders et al, 1996), GABA (Bianchi et al, 1994(Bianchi et al, , 1996Kendrick et al, 1996), and Tau (Bianchi et al, 1996).…”

Glutamate receptor activation induces carrier mediated release of endogenous GABA from rat striatal slices

“…It has been shown that glutamatergic activation induces CaZ+-dependent and CaZ+-independent release of [3H] GABA from cultured neurons from striatum (Pin and Bockaert, 1989;Weiss, 1988) hippocampus (Harris and Miller, 1989) and cortex (Drejer and Honore, 1987). Recently, Young and Bradford reported that a NMDA stimulated [14C]GABA release from rat striatum in an in vivo microdialysis paradigm (Young and Bradford, 1993). Each of the experiments cited above were carried out in the presence of a GABA transaminase inhibitor that was included to protect the labelled GABA from metabolism during loading.…”

In Vivo Electrochemical Measurement of the Long‐Lasting Release of Dopamine and Serotonin Induced by Intrastriatal Kainic Acid

“…This suggests that administration of 5-HI antagonists may be effective in the treatment of Huntington's disease patients. It has been proposed (Young et al, 1988;Ruzicka and Jhamandas, 1991;Young and Bradford, 1993) that release of other transmitters, e.g., GABA, glutamate, and peptides, also occurs after administration of KA. This finding also suggests that these transmitter antagonists may be effective in this disease.…”