Increasing amounts (0.3–12 mg/kg) of kainic acid (KA) were given intravenously to rats and behavioral, electrographic, 2-deoxyglucose autoradiographic and neuropathologic responses were studied. A dose of 12 mg/kg kainic acid caused a stereo-typed sequence of staring spells, wet dog shakes, automatisms — mild limbic convulsions and severe limbic convulsions (rearing, bilateral upper extremity clonus, falling and salivation) that developed over 1–2 h. Smaller doses showed different thresholds for these behavioral phenomena but a similar time course of development. Electrographic seizures in limbic areas were similar to afterdischarges produced with electrical stimulation and their threshold was 4 mg/kg. The earliest electrical changes occurred in the hippocampus and were accompanied by staring spells. Subsequently seizures were synchronized in limbic centers during which mild convulsive activity was seen. Finally electrical seizures appeared in both limbic and surface leads, coincident with severe convulsions. Quantitative deoxyglucose autoradiography showed that the hippocampul CA₃ region was most sensitive to metabolic changes. Mild limbic convulsions were associated with increased glucose utilization in the hippocampus, subiculum, pyriform and entorhinal cortices, septum and amygdala. Severe limbic convulsions led to even larger changes in these areas as well as the substantia nigra and part of the thalamus. Neuronal damage was seen without systemic metabolic derangements with a threshold of 7 mg/kg. The regions of neuropathology overlapped with areas of intense seizure activity.

These data show that systemic kainic acid preferentially activates seizures in the limbic system, particularly the hippocampus, and that different behavioral concomitants of limbic seizures depend on specific patterns of activation of limbic and extra limbic circuits. A scheme for the anatomic spread of seizures in limbic and non-limbic structures is proposed. A state of ‘limbic status’ underlies the neurotoxicity of kainic acid.