Production of extracellular quinolinic acid in the striatum studied by microdialysis in unanesthetized rats

Striatal microdialysis was performed in awake rats in an attempt to produce extracellular quinolinic acid (QUIN) from its putative bioprecursors L-tryptophan, L-kynurenine and 3-hydroxyanthranilic acid (3HANA). Test compounds were included in the microperfusion solution. QUIN concentrations in the dialysate remained below the assay sensitivity (i.e. less than 20 nM) under baseline conditions or after extensive perfusion with 1 mM L-tryptophan or L-kynurenine. 3HANA (10-300 microM) caused dose-dependent increases in extracellular QUIN, which attained steady-state concentrations after 4 h. The initial rate of QUIN production was significantly increased in the ibotenate-lesioned striatum, suggesting a pivotal role of astroglia in the deposition of brain QUIN.