Synergistic effects of chronic exposure to subthreshold concentrations of quinolinic acid and malonate in the rat striatum.
Adult rats received chronic intrastriatal dialytic exposure to quinolinic acid (QUIN), malonate, or a combination of QUIN and malonate. The combination of subthreshold concentrations of QUIN (4 mM) and malonate (400 mM) produced lesions larger than did either QUIN or malonate alone. The neurotoxic effect of QUIN combined with malonate was subsequently blocked by co-administration of the NMDA receptor antagonist MK-801 (1 mM). These findings indicate that malonate synergistically enhances NMDA receptor mediated excitotoxicity.
Bazzett
T J
TJ
Department of Neurology, University of Michigan, Ann Arbor 48104-1687, USA. tbazzett@urich.edu
Falik
R C
RC
Becker
J B
JB
Albin
R L
RL
D000818:Animals; D003956:Dialysis; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004357:Drug Synergism; D003576:Electron Transport Complex IV / Q000378:metabolism; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D008297:Male; D008314:Malonates / Q000633:toxicity*; D016202:N-Methylaspartate / Q000633:toxicity; D009252:NADPH Dehydrogenase / Q000378:metabolism; D017072:Neostriatum / Q000187:drug effects*; D009498:Neurotoxins / Q000633:toxicity; D011805:Quinolinic Acids / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors
D018691:Excitatory Amino Acid Antagonists; D008314:Malonates; D009498:Neurotoxins; D011805:Quinolinic Acids; D016194:Receptors, N-Methyl-D-Aspartate; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; C030290:malonic acid; D009252:NADPH Dehydrogenase; D003576:Electron Transport Complex IV