Changes in extracellular kynurenic acid concentrations in rat prefrontal cortex after D-kynurenine infusion: an in vivo microdialysis study.
Using a microdialysis technique, we continuously infused D-kynurenine (KYN) (0, 50, and 100 microM) 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 alpha7 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.
Ogaya
Tadahiro
T
Department of Analytical Chemistry, Faculty of Pharmaceutical Sciences, Toho University, Funabashi-shi, Chiba, Japan.
Song
Ziyu
Z
Ishii
Kana
K
Fukushima
Takeshi
T
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D007736:Kynurenic Acid / Q000378:metabolism*; D007737:Kynurenine / Q000008:administration & dosage*; D008297:Male; D017551:Microdialysis; D017397:Prefrontal Cortex / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013050:Spectrometry, Fluorescence
D007737:Kynurenine; D007736:Kynurenic Acid