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.