Domoic acid (DOM) is a potent agonist of AMPA and kainic acid (KA) receptor
s in the CNS and is known to produce seizures acutely, and lasting excitoto
xic damage in several brain regions, While the excitotoxic effects of DOM a
re well documented, its seizurogenic properties are less clear. In this stu
dy, we assessed the acute effects of DOM and KA in region CA1 of intact rat
hippocampal slices (CA3-on) and in slices lacking region CA3 (CA3-off). Or
thodromic Schaffer collateral-evoked CA1 field potentials (population spike
s and somal EPSP's) were monitored during DOM and KA (10-500 nM) administra
tion. In CA3-off slices both KA and DOM produced immediate increases in CA1
population spike amplitude. With prolonged exposure, lasting dose-dependen
t reductions in spike amplitude and EPSP slope were observed, possibly due
to depolarising conduction block following excessive AMPA/KA receptor activ
ation DOM was several-fold more potent than KA in this regard. Population s
pike threshold did not vary with DOM, but in CA3-on slices a dose-dependent
steepening of the I/O curve and increase in maximum spike amplitude was se
en. CA1 hyperexcitability, as evidenced by the appearance of prominent seco
nd and third population spikes, was equivalently increased across a range o
f DOM concentrations in both CA3-on and CA3-off slices and. in general, DOM
-induced CA1 hyperexcitability was not enhanced by the presence of CA3 for
any of the other variables assessed in this study. These findings show that
DOM directly promotes neuronal hyperactivity in region CA1, presumably due
to tonic AMPA and/or KA-receptor mediated depolarization, and further sugg
ests that DOM-induced hyperactivity in the recurrently networked, AMPA/KA-r
eceptor rich region CA3 does not contribute to the onset and spread of limb
ic seizures during relatively mild DOM intoxication. (C) 2001 Elsevier Scie
nce B.V. All rights reserved.