Electroclinical and pathological studies after parenteral administration of domoic acid in freely moving nonanesthetized rats: An animal model of excitotoxicity

We examined the excitotoxic effect of domoic acid (DA) on freely moving rats. Bipolar electrodes were stereotaxically placed in the dorsal hippocampus of 20 male Wistar rats under pentobarbital anesthesia. Skull screws were placed over the sensorimotor cortex. Animals were allowed 8 days to recover from surgery. They were divided into four groups and, while awake, received intraperitoneal phosphate buffer solution (group A 2 ml), or DA (group B 1 mg/kg, group C 5 mg/kg, group D 10 mg/kg). Video-EEG monitoring was performed for 24 h after injection of DA. In group B, focal hippocampal seizure status was induced ~2 h after injection. These seizures were reversible and subsided ⩽6 h after injection of DA. In groups C and D, severe limbic seizure status was induced, which progressed to fatal generalized status epilepticus. The clinical manifestations correlated well with the EEG changes. Pathologic examination disclosed dose-dependent hippocampal damage in groups B, C, and D and additional cortical damage in group D. Systemic administration of DA induced not only excessive hippocampal excitation but also severe hippocampal damage. This animal model provides further evidence supporting the role of excitotoxic injury in epileptogenesis and may be useful in developing protective mechanisms against hippocampal excitotoxicity.