Behavioral and electrographic patterns induced by systemic administration of kainic acid in developing rats.

Abstract

Abstract Behavioral and electrographic changes induced by systemic injection of 3–6 mg/kg of kainic acid (KA) have been studied during development in 1- to 28-day-old rats. In the first week of life, a few minutes after the administration of the toxin, animals developed motor signs such as scratching movements, hypo- and hyperactivity, loss of postural control, tremors and hyperextension of the limbs. No changes of the electrical cortical and hippocampal activity were detected. Similar, but more accentuated motor signs occur when KA was injected during the second week of postnatal life. In this case, on the electroencephalogram (EEG), bursts of spikes or polispikes localized in the cortex appeared. These bursts became more and more frequent and after only 20 min spread to the hippocampus. No correlation between the electrical and behavioral changes were observed. By the third week of life, in addition to motor signs, systemic kainic acid induced wet dog shakes (WDS) and limbic seizures. These were characterized by rearing, loss of postural control, masticatory movements and forepaw tremors. The EEG was characterized by primary hippocampal discharges that may spread to the cortex. Usually the limbic seizures become more and more frequent, leading to a status epilepticus. In another group of experiments, higher doses of KA (6–12 mg/kg) have been injected in curarized and artificially respirated animals of the same age. During the first days of life (1–7), unlike in the corresponding group of freely moving animals, KA induced sequences of slow spikes localized in the cortex and after 10–20 min spread to the hippocampus. In the following age-groups no differences between the curarized and free moving animals were detected. The different sensitivity of systemic KA to induce limbic seizures in neonatal rats may be related to the immaturity of pre- and post-synaptic glutamergic receptors in the hippocampus. Moreover, a different degree of maturity of cortical versus hippocampal glutamergic receptors may account for the preferential activation of the cortex versus hippocampus during the first period of life.