Abstracts

Rationale: The involvement of the thalamus in limbic epileptogenezis has recently drawn attention to the connectivity between the nuclei of the thalamus and limbic structures. Thalamo-limbic circuits are thought to regulate limbic seizure activity whereas thalamocortical circuits are involved in the expression and generation of spike-and-wave discharges (SWDs) in the absence epilepsy models. Kindling as a model of temporal lobe epilepsies is a well known model which is firing the hippocampal neurons and causes seizures in rats. Recent studies showed that there is a resistance in the duration of behavioral changes in the kindling process and the relation of SWD activity to the kindling progress in the GAERS and WAG/Rij animals (1, 2) Gamma-Hydroxybutyric acid (GHB) produces a constellation of EEG and behavioural changes when given to animals, which represent an chemical experimental model of generalized absence seizures (3). In this study we aimed to determine whether the resistance to the development of kindling in absence epilepsy can be independent of the genetic background. Methods: We used adult male Wistar rats weighing 250-300 gr. The animals were anesthetized with ketamine and chlorpromazine. The head of each animal was placed in a stereotaxic instrument and stainless steel electrodes were implanted into the right basolateral amygdala and into the skull for stimulation and recording. All of the electrodes were fixed to the skull with dental acrylic. After a recovery period, a baseline EEG was recorded for at least 30 min from all rats. Thereafter the animals were grouped as a GBL injected group (GBL), a GBL injected and kindling stimulated group (GBL-KI) and a kindling (KI) group. The after discharge thresholds were determined for KI and GBL-KI groups. The KI group was stimulated twice daily at the after discharge threshold; the GBL-KI group was also stimulated twice daily, each at 20 min after the intraperitoneal GBL injection, until they reached Racine’s stage 5 seizure state. The GBL group had intraperitoneal injections twice a day. EEG recordings were performed for all the groups at least 90 min. Results: The seizure stages and SWD periods were determined in all groups. The KI animals had stage 5 seizures by 15 stimulations. However, the GBL-KI group had stage 4 or 5 seizures by 30 stimulations. Our data show that there is a delay in the development of kindling as well as a relation of SWD activity to the kindling progress after GBL administration. Conclusions: The resistance to limbic epilepsy in absence epilepsy rats seems to be partially influenced by the absence epilepsy itself and possibly also be the genetic background. 1) Onat et al., Epilepsia 2007, 48(12):2381 2) Gurbanova et al., J Neuroscience 2008, 30;28(31):7828-36, 3) Snead OC 3rd., Neuropharmacology 1991, 30(2):161-7