Circumventricular organ origin of domoic acid-induced neuropathology and toxicology.

The neuroexcitotoxin, domoic acid, was responsible for an episode of mussel poisoning in Eastern Canada in 1987. Severe neurologic impairment and some deaths occurred. We have characterized the nature of domoate-induced neuropathology in the mouse brain. Domoic acid was administered intraperitoneally at doses of 2, 3 or 7 mg/kg to Swiss-Webster mice. Brains were examined at 0.5, 1, 24, 48 or 72 h postinjection for evidence of damage. Significant pathologic changes occurred only after the largest dose of domoic acid. Damage was confined to circumventricular organs lacking a blood-brain barrier and their environs, including the organon vasculosum of the lamina terminalis, subfornical organ, mediobasal hypothalamus and area postrema. The neural damage induced by domoic acid was evident at as early as 30 min after injection and increased by 60 min postinjection. The loci of domoic acid-induced neuropathological changes accounts for several central and peripheral effects and toxicities observed following systemic domoate treatment, these included gastroduodenal lesions, hypodipsia, analgesia, and blood pressure fluctuations.