Chronic exposure of kainate and NBQX changes AMPA toxicity in hippocampal slice cultures

Receptor agonist/antagonist mediated modulation of the excitotoxic effect of AMPA was studied in organotypic hippocampal slice cultures. Treatment of developing cultures for 2 weeks with a subtoxic dose of 2 muM kainate reduced the toxicity of 3 muM AMPA, applied for 48 h with 24 h of recovery, as measured by cellular uptake of the fluorescent dye propidium iodide. In contrast long-term treatment with 0.3 muM of the AMPA/KA antagonist NBQX increased the susceptibility of the cultures to an even lower dose of 2 muM AMPA. The modulatory effects of long-term application of low doses of kainate and NBQX, have implications for the development and use of related drugs that aim to protect against glutamate receptor-mediated disturbances. (C) 2001 Lippincott Williams & Wilkins.