Jakobsen B, Zimmer J
Neuroscience PharmaBiotec, Anatomy and Neurobiology, Institute of Medical Biology, SDU-Odense University, Winsloewparken 21, DK-5000 Odense C, Denmark.
Neuroreport. 2001 Nov 16;12(16):3593-7. doi: 10.1097/00001756-200111160-00044.
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 microM kainate reduced the toxicity of 3 microM 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 microM of the AMPA/KA antagonist NBQX increased the susceptibility of the cultures to an even lower dose of 2 microM 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.