Maturation of kainic acid seizure-brain damage syndrome in the rat. I. Clinical, electrographic and metabolic observations

The maturation of the seizure/brain damage syndrome produced by parenteral administration of kainate was studied in the rat. The motor, electrographic and metabolic alterations are described in the present report, the maturation of the pathological abnormalities and of the specific kainate binding sites are described in the two following companion papers. Parenteral kainate produces tonico-clonic seizures until the end of the third week of age when limbic motor signs (wet-dog shakes, facial myoclonia, paw tremor etc.) were first produced. Using the 2-deoxyglucose autoradiographic method, we found that in animals of 3 days of age and until the third week of age, kainate produced a rise in metabolism restricted to the hippocampus and lateral septum. This was paralleled by paroxysmal discharges which were recorded in the hippocampus. Starting from the end of the third week of age approximately--i.e. when the toxin produced limbic motor seizures--there was a rise of labelling in other structures which are part of or closely associated to the limbic system i.e. the amygdaloid complex, the mediodorsal and adjacent thalamic nuclei, piriform, entorhinal and rostral limbic cortices and areas of projection of the fornix. These metabolic maps are thus similar to those seen in adults. Two main conclusions can be drawn from these experiments: kainate activates the hippocampus from a very early age probably by means of specific receptors present in this structure and the limbic syndrome will only be produced by the toxin once the limbic circuitry--including in particular the amygdaloid complex--is activated by the procedure i.e. after the third week of age.