Absence and mixed forms of epilepsy in WAG/Rij rats : characteristics and brain aminergic modulations

Abstract

The neuroanatomical substrates of absence seizures and convulsive seizures differ; absence seizures are generated in the cortico-thalamic loop, whereas the brain stem and limbic structures are involved in audiogenic convulsive seizures. In spite of this difference, the two seizure types share a major precipitating factor: emotional stress, although absence seizures are more likely to be provoked by stress than other types of epileptic seizures. This implies that mechanisms of stress vulnerability are at least partly different in brains with convulsive and non-convulsive seizures. The response of an organism to stressors greatly depends on its brain aminergic functions. Therefore, it is hypothesized that the tone of the brain aminergic system in absence epileptic subjects is different from that of non-epileptic controls. This could lead to a poor ability of coping with stress. In the presented studies, genetic animal models to investigate putative impacts of the seizure type and severity on behavioral traits and brain aminergic indices were used. WAG/Rij rats (genetically prone to absence seizures) and Wistar rats (more resistant to absence epilepsy), both with and without susceptibility to audiogenic convulsions, were compared. Absence and audiogenic seizures were scored, in order to unmask putative effects of seizures' severity on behavioural traits and brain aminergic neurochemistry. In additional experiments, the distribution of several types of brain amine receptors (dopamine, histamine) were studied and effects of drugs affecting the aminergic neurotransmission (haloperidol, pyrilamine) were assessed in WAG/Rij rats. The major outcome of the experiments described in the thesis is that absence seizures affect the brain aminergic indices outside the thalamocortical loops, and/or that strength of the brain aminergic tone might suppress or facilitate the occurrence of absence seizures. It is also proposed that the seizure-related changes in neurochemistry of the limbic system might underlie an enhanced stress vulnerability of absence epileptic patients and rats.