Ketamine, but not glycine modulates quinolinate-induced neurodegeneration.
The influence of ketamine and glycine on the neurotoxicity of the N-methyl-D-aspartate-(NMDA)-receptor agonist quinolinic acid [QUIN; injected intracerebroventricularly (icv)] was studied in rats. Ketamine, an NMDA-receptor antagonist prevented completely the QUIN-induced hippocampal damage at a dosage of 40 mg/kg (140 mumol/kg, intraperitoneally applied). Glycine, a physiological co-agonist of the NMDA-receptor, was applied icv in addition to QUIN. Even at high doses (up to 1.33 mumol) glycine did not show any effects on QUIN neurotoxicity, if the neurotoxin was administered at a subliminal dose (0.25 mumol). The apparent lack of a potentiating effect of exogenously applied glycine favors the assumption that glycine binding sites are saturated under physiological conditions.
Henschke
G
G
Institute of Medical Neurobiology, University of Magdeburg, Germany.
Wolf
G
G
Keilhoff
G
G
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D005998:Glycine / Q000008:administration & dosage / Q000494:pharmacology*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000473:pathology; D007274:Injections, Intraperitoneal; D007276:Injections, Intraventricular; D007649:Ketamine / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009410:Nerve Degeneration / Q000187:drug effects*; D017966:Pyramidal Cells / Q000187:drug effects* / Q000473:pathology; D017378:Quinolinic Acid / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar
D007649:Ketamine; D017378:Quinolinic Acid; D005998:Glycine