Neuroexcitatory and neurotoxic actions of the amnesic shellfish poison, domoic acid

We have investigated the action of domoic acid in the mouse brain following systemic exposure. Domoic acid increased c-fos mRNA within 15 min and its translational product (c-Fos) within 1 h. c-Fos immunoreactivity was most prominent in the hippocampal formation, lateral septal nucleus, olfactory bulb, area postrema and the nucleus of the solitary tract. We next examined irreversible toxic effects of domoic acid. Domoic acid caused extensive degeneration in CA1-2 of the hippocampus, lateral septal nucleus and olfactory bulb. No degeneration was evident in the dentate gyrus or brain stem. These studies demonstrate that domoic acid has only neuroexcitatory effects on brain stem regions associated with visceral function whereas it has permanent neurotoxic effects on brain regions associated with memory formation.