Intrahippocampal injections of ibotenic acid provide histological evidence for a neurotoxic mechanism different from kainic acid.

Stereotaxic injections of ibotenic acid (IBO) and kainic acid (KA) into either the dorsal hippocampus or the lateral cerebroventricle were performed in order to determine the relative potencies of the drugs and the vulnerability of different hippocampal cell types to their neurotoxic action, IBO was found to be approximately five times less potent than KA in causing degeneration of hippocampal neuronal cell bodies. Unlike KA (0.5 and 1.0 microgram), IBO (5.0 micrograms) caused few signs of intrahippocampal bleeding or necrosis of non-neuronal elements. Pyramidal cells of the CA3 and CA4 regions were the most sensitive and dentate granule cells the least sensitive to KA. In contrast, IBO cused degeneration of granule cells and CA3/CA4 pyramids to an equal extent.