Suppression of domoic acid induced seizures by 8-(OH)-DPAT

Microinjections of the neuroexcitotoxin, domoic acid (DOM), in the ipsilateral rat hippocampal CA-3 region, induced generalized electrical seizure discharge activity, characterized by spikes and waves, followed by intermittent burst discharges. Computerized EEG analysis exhibited relative dominance of delta and theta and reductions in alpha and beta activities during domoic acid epileptogenesis. Seizure discharge activity was attenuated by the microinjection of the 5-HT1A agonist, 8-hydroxy-2-(di-N-propylamino)tetralin(8-(OH)-DPAT) and augmented by the specific 5-HT1A antagonist, spiroxatrine in the contralateral hippocampal CA-3 region. Neuronal recovery following 8-(OH)-DPAT was associated with significant reductions in the relative dominance of delta and theta and increases in the alpha and beta activities. The results suggest that activation of serotonergic 5-HT1A receptor in the hippocampus has a neuroprotective action.