The effects of intrahippocampal ibotenic acid and their blockade by (-) 2-amino-7-phosphonoheptanoic acid: Morphological and electroencephalographical analysis

Intrahippocampal injections of the excitotoxin ibotenic acid caused a biphasic behavioral pattern in rats. Both the immediate induction of hyperactivity and stereotypical behaviors and a secondary phase of progressively decreasing behavioral activities beginning 15-20 min after ibotenate administration, were accompanied by characteristic seizures measured by bilateral recordings in hippocampus and cortex. Typically, EEG changes consisted of high voltage spiking in all leads. The phase of behavioral depression was accompanied by episodic, short (5-30 s) seizures. In addition, cortical slow waves very similar to those elicited by intrahippocampal muscimol were observed during this period. Attempts were made to correlate occurrence and severity of seizures with the extent of neuronal degeneration. While a trend in favor of such a correlation existed, a firm causal relationship could not be established: some animals could display seizure activity with only marginal concomitant nerve cell loss and vice versa. Intrahippocampal co- and post-administration of ibotenate with (-) 2-amino-7-phosphonoheptanoic acid entirely prevented or stopped the occurrence of both EEG changes and neuronal degeneration. Ibotenate-induced seizures and lesions and their specific blockade by a selective antagonist may constitute valuable experimental paradigms for the investigation of seizure disorders.