Acute neurotoxicity of domoic acid in the rat

A recent outbreak of human food poisoning, characterized by severe gastrointestinal and neurologic abnormalities, with a fatal outcome in 3 patients, was attributed to the consumption of poisonous mussels containing domoic acid at an abnormally high concentration. The purpose of the present study was to determine if domoic acid, a glutamate analogue extracted from poisonous mussel, was neurotoxic to rats. Groups of female Sprague-Dawley rats were dosed once intraperitoneally with 0, 1, 2, 4, or 7.5 mg domoic acid/kg of body weight and observed for a maximum period of 24 hr. Clinically, control rats and rats in the 1 mg/kg group were unremarkable. Seventy-five percent of the animals in the 2 mg/kg group had equivocal transient behavioral signs. One that was given 2 mg/kg and all rats given in excess of 4 mg/kg of body weight developed unequivocal behavioral and neurologic signs culminating in partial seizures and status epilepticus. Histopathologically, severely affected rats developed selective encephalopathy characterized by neuronal degeneration and vacuolation of the neuropil in the limbic and the olfactory systems, and retinopathy characterized by neuronal hydropic degeneration of the inner nuclear layer and vacuolation of the external plexiform layer. The results of this study suggest that domoic acid is excitotoxic and causes a characteristic syndrome with clinical signs and histopathologic lesions similar to those reported for kainic acid.