Determination of extracellular kynurenic acid in the striatum of unanesthetized rats: effect of aminooxyacetic acid.
Kynurenic acid (KYNA) production from its bioprecursor L-kynurenine (KYN) was assessed in vivo by intrastriatal microdialysis in freely moving rats. In the absence of KYN, the extracellular concentration of KYNA was below the limit of assay sensitivity (i.e. less than 8 pmol/30 microliters). In the presence of KYN (50-2000 microM), KYNA concentration in the dialysate increased continuously to reach steady-state levels after 2h of perfusion. Introduction of the unspecific transaminase inhibitor aminooxyacetic acid (AOAA) through the dialysis probe caused a progressive decrease of extracellular KYNA, which reached dose-dependent minimal levels within 2 h. One mM AOAA caused an almost complete depletion of KYNA in the dialysate. These data demonstrate that extracellular KYNA can be assessed by microdialysis and that AOAA can be used as a tool to examine the neurobiology of KYNA in awake, freely moving animals.
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Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore 21228.
Wu
H Q
HQ
Gramsbergen
J B
JB
Turski
W A
WA
Ungerstedt
U
U
Schwarcz
R
R
D000625:Aminooxyacetic Acid / Q000494:pharmacology*; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D003956:Dialysis / Q000379:methods; D004305:Dose-Response Relationship, Drug; D007700:Kinetics; D007736:Kynurenic Acid / Q000378:metabolism*; D007737:Kynurenine / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D000625:Aminooxyacetic Acid; D007737:Kynurenine; D007736:Kynurenic Acid