Changes in Extracellular Kynurenic Acid Concentrations in Rat Prefrontal Cortex After d-Kynurenine Infusion: An In vivo Microdialysis Study
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Using a microdialysis technique, we continuously infused d-kynurenine (KYN) (0, 50, and 100 μM) into the prefrontal cortices (PFCs) of male Sprague–Dawley rats. We then used column-switching high-performance liquid chromatography to assess the alterations in the concentration of kynurenic acid (KYNA)—an antagonist of N-methyl-d-aspartate and α7 nicotinic acetylcholine receptors—in the extracellular fluid in the PFC. Local infusion of d-KYN into the PFC remarkably increased the extracellular KYNA concentration, indicating that d-KYN is metabolized to KYNA in the PFC. The d-KYN-induced increase in KYNA levels was significantly attenuated by the co-administration of 3-methylpyrazole-5-carboxylic acid (AS057278)—a specific inhibitor of d-amino acid oxidase (DAAO). These results suggest that DAAO may be involved in the production of KYNA from d-KYN in the PFC in vivo.
Keywordsd-Kynurenine Kynurenic acid Brain microdialysis d-Amino acid oxidase Column-switching high-performance liquid chromatography
We thank Dr. M. Sato, Toho University, for his helpful discussions on this study.
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