The aim of this study was to investigate the effect of arachidonic aci
d on [H-3]d-aspartate outflow in rat hippocampus synaptosomes and slic
es. Arachidonic acid 1) increased basal outflow of [H-3]d-aspartate in
both synaptosomes and slices, and 2) increased K+-evoked overflow in
slices but not in synaptosomes. The latter effect was dependent (at le
ast in part) on arachidonic acid metabolism, most likely mediated by l
ipo-oxygenase metabolites and flee radical production. It was prevente
d by nordihydroguaiaretic acid but not by indomethacin, and was signif
icantly reduced by free radical scavengers (superoxide-desmutase and c
atalase). This effect was dependent upon stimulation since it could no
t be observed after a continuous perfusion of arachidonic acid in the
absence of stimulation. Furthermore, it was long-lasting since a 30 mi
n perfusion of arachidonic acid was sufficient to exert a significant
effect on a stimulation following termination of the application.