A comparative histological and electrophysiological study of some neurotoxins in the rat hippocampus

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Abstract
It has been proposed that the neurotoxic action of kainic acid is a result of the seizure activity which it induces. In this study intraventricular injection of kainic acid, and three other putative neurotoxins, was used in an attempt to investigate the role of electrical seizure activity and neurotoxicity in the rat hippocampus, Two separate groups of experiments were performed. First, & histological study of the neurotoxic potency of the compounds under investigation was carried out, and second, an electrophysiological study of those compounds which displayed neurotoxicity. In these experiments, extracellular recordings were made in the hippocampus ipsilateral to infusion during and after administration of the neurotoxin.Kainic acid (5.0 μg) produced unilateral lesions of the CAB and C A4/ hilus cells of the hippocampus, but CA1 and granule cells remained intact. Electrical seizure activity could be recorded from both CS3 and CA1 regions after kainic acid infusion. Dihydrokainic acid displayed no neurotoxicity. α‐ketokainic acid (5.0 μg) only produced minor toxic effects such as small areas of pyknosis, but electrical seizure activity was produced in both CA3 and CA1 cell regions. Cis 1‐amino 1,3‐dicarboxycyclopentane (cis‐ADCP), (5.0 μg) produced unilateral lesions of the CA3 area without any extension into the CA4/hilus cell layer. There was no electrical seizure activity associated with the action of this compound.These results show that the presence of seizure activity in the hippocampus is not invariably followed by loss of pyramidal cells. As cis‐ADCP produces a discrete lesion in the absence of any seizure activity, this compound may prove to be a more useful neurotoxin for producing experimental models of disease states in the central nervous system.