Systemic d-amphetamine administration causes a reduction of kynurenic acid levels in rat brain.
Tissue levels of the endogenous excitatory amino acid receptor antagonist kynurenic acid (KYNA) and of its bioprecursor L-kynurenine were measured in rats of different ages after d-amphetamine administration. In adult animals, extracellular KYNA concentrations were also determined in vivo by hippocampal microdialysis. In the adult brain, d-amphetamine caused a transient, dose-dependent decrease in tissue content and extracellular levels of KYNA, reaching a nadir of approximately 70% of control values after 1 h at 5 mg/kg. Quantitatively similar decrements were observed in four different brain regions. Seven, 14 and 28-day-old pups were particularly sensitive to the drug, showing a reduction in forebrain KYNA levels to 25%, 40% and 35% of control values, respectively, 1 h after the administration of 5 mg/kg d-amphetamine. Notably, no changes in brain L-kynurenine levels and in liver L-kynurenine and KYNA concentrations were found after d-amphetamine administration. Thus, endogenous monoamines released by d-amphetamine may interfere with the transamination of L-kynurenine to KYNA specifically in the brain. These results suggest that d-amphetamine increases excitatory amino acid receptor function temporarily by reducing the levels of endogenous KYNA.
Rassoulpour
A
A
Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore 21228, USA.
Wu
H Q
HQ
Poeggeler
B
B
Schwarcz
R
R
D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003913:Dextroamphetamine / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000378:metabolism*; D005110:Extracellular Space / Q000378:metabolism; D007736:Kynurenic Acid / Q000037:antagonists & inhibitors*; D007737:Kynurenine / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
D000697:Central Nervous System Stimulants; D018691:Excitatory Amino Acid Antagonists; D007737:Kynurenine; D007736:Kynurenic Acid; D003913:Dextroamphetamine