1. Modulation and function of kynurenic acid in the immature rat brain.
- Author
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Schwarcz R, Ceresoli-Borroni G, Wu HQ, Rassoulpour A, Poeggeler B, Hodgkins PS, and Guidetti P
- Subjects
- 2-Amino-5-phosphonovalerate analogs & derivatives, 2-Amino-5-phosphonovalerate pharmacology, Aging metabolism, Alanine analogs & derivatives, Alanine pharmacology, Animals, Brain drug effects, Brain growth & development, Dextroamphetamine pharmacology, Enzyme Inhibitors pharmacology, Excitatory Amino Acid Antagonists pharmacology, Glucose metabolism, Kynurenine 3-Monooxygenase, Male, Microdialysis, Mixed Function Oxygenases antagonists & inhibitors, N-Methylaspartate pharmacology, Neurons drug effects, Neurons physiology, Pyruvates pharmacology, Rats, Rats, Sprague-Dawley, Brain physiology, Kynurenic Acid metabolism
- Abstract
Using in vivo and in vitro paradigms, the regulation and function of the brain metabolite kynurenic acid (KYNA) was examined in rats on postnatal days (PND) 7 and 14. As shown previously in adult rats, glucose removal and d-amphetamine (d-Amph) administration caused decreases in KYNA formation, while exposure to pyruvate up-regulated KYNA synthesis. The effect of glucose deprivation was substantially blunted in immature animals. In PND 14 rats, d-Amph pre-treatment exacerbated the excitotoxic effects of an intrastriatal N-methyl-D-aspartate (NMDA) injection. This potentiation was prevented by m-nitrobenzoylalanine, a kynurenine 3-hydroxylase inhibitor that also antagonized the KYNA reduction caused by d-Amph. These and additional experiments with the competitive NMDA receptor antagonist CGP 40116 indicate the existence of a functionally significant, novel high-affinity receptor for KYNA in the brain.
- Published
- 1999
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