BIPHASIC EFFECT OF HYDROGEN-PEROXIDE ON FIELD POTENTIALS IN RAT HIPPOCAMPAL SLICES

In the CA1 region of rat hippocampal slices, H2O2 (0.294-2.94 mM) caus ed initial augmentation, and subsequent long-lasting depression, of po pulation spikes and excitatory postsynaptic potentials. The effect of H2O2 may not be mediated by its degradation product, hydroxyl radicals , because an iron chelator deferoxamine did not block the effect. A ca talase inhibitor 3-amino-1,2,3-triazole only modestly attenuated the i nitial augmentation, suggesting that the effect of H2O2 is not attribu table to catalase-dependent O-2 generation, either. An N-methyl-D-aspa rtate receptor antagonist DL-2-amino-5-phosphonovaleric acid had no in fluence on the effect of H2O2, whereas a gamma-aminobutyric acid type A receptor channel blocker picrotoxin attenuated long-lasting depressi on, indicating that gamma-aminobutyric acid-mediated inhibition is alt ered during the depression phase. The initial augmentation but not sub sequent depression was attenuated by a phospholipase A(2)/C inhibitor 4-bromophenacyl bromide, suggesting the involvement of lipid signaling molecule(s) in the enhancement of excitatory synaptic transmission. T hese results suggest that H2O2 regulates hippocampal synaptic transmis sion via multiple mechanisms. (C) 1997 Elsevier Science B.V.