ON THE ORIGIN OF EXTRACELLULAR GLUTAMATE LEVELS MONITORED IN THE BASAL GANGLIA OF THE RAT BY IN-VIVO MICRODIALYSIS

Several putative neurotransmitters and metabolites were monitored simu ltaneously in the extracellular space of neostriatum, substantia nigra , and cortex and in subcutaneous tissue of the rat by in vivo microdia lysis. Glutamate (Glu) and aspartate (Asp) were at submicromolar and g amma-aminobutyric acid (GABA) was at nanomolar concentrations in all b rain regions, The highest concentration of dopamine (DA) was in the ne ostriatum. Dynorphin B (Dyn B) was in the picomolar range in all brain regions. Although no GABA, DA, or Dyn B could be detected in subcutan eous tissue, Glu and Asp levels were approximate to 5 and approximate to 0.4 mu M, respectively. Lactate and pyruvate concentrations were ap proximate to 200 and approximate to 10 mu M in all regions. The follow ing criteria were applied to ascertain the neuronal origin of substanc es quantified by microdialysis: sensitivity to (a) K+ depolarization, (b) Na+ channel blockade, (c) removal of extracellular Ca2+, and (d) d epletion of presynaptic vesicles by local administration of alpha-latr otoxin. DA, Dyn B, and GABA largely satisfied all these criteria. In c ontrast, Glu and Asp levels were not greatly affected by K+ depolariza tion and were increased by perfusing with tetrodotoxin or with Ca2+-fr ee medium, arguing against a neuronal origin. However, Glu and Asp, as well as DA and GABA, levels were decreased under both basal and K+-de polarizing conditions by alpha-latrotoxin. Because the effect of K+ de polarization on Glu and Asp could be masked by reuptake into nerve ter minals and glial cells, the reuptake blocker dihydrokainic acid (DHKA) or L-trans-pyrrolidine-2,4-dicarboxylic acid (PDC) was included in th e microdialysis perfusion medium. The effect of K+ depolarization on G lu and Asp levels was increased by DHKA, but GABA levels were also aff ected. In contrast, PDC increased only Glu levels. It is concluded tha t there is a pool of releasable Glu and Asp in the rat brain. However, extracellular levels of amino acids monitored by in vivo microdialysi s reflect the balance between neuronal release and reuptake into surro unding nerve terminals and glial elements.