Intrahippocampal injection of kainic acid produces significant pyramidal cell loss in neonatal rats.

Previous reports have indicated that pyramidal cells in the developing rat hippocampal formation are not destroyed by intraventricular or intraperitoneal administration of kainic acid. We examined the neurotoxic properties of kainic acid and ibotenic acid following intrahippocampal injection in neonatal rats and found significant pyramidal cell death following injection of 1.0 microgram kainic acid in 6, 7 and 9-day-old pups. At doses 2.5 or five times this amount, significant pyramidal cell loss was obtained in 5-day-old rats as well. The susceptibility of pyramidal neurons to kainic acid increased as a function of age. The developing hippocampus was considerably more vulnerable to ibotenic acid compared with kainic acid, in contrast to the order of potency reported in adult rats. The increased sensitivity of CA3 pyramidal cells parallels the development of the mossy fiber innervation to the dendrites of these cells supporting the twofold mechanism suggested by Coyle for kainic acid neurotoxicity; that is, a direct cytotoxic action via postsynaptic receptors as well as increased sensitivity due to the presence of excitatory inputs.