The genetically epilepsy-prone rat

Abstract

1. 1. The genetically epilepsy-prone rat (GEPR) is a valuable model for investigating mechanisms involved in epilepsy because of the controllable nature of the convulsions and their genetic origin. 2. 2. The GEPR exhibits audiogenic seizures (AGS) and also displays higher than normal sensitivity to convulsant drugs, kindling, electroshock and hyperthermic seizures. 3. 3. An abnormal electroencephalographic pattern and increased thresholds for auditory evoked potentials from the cochlea and brainstem are observed in the GEPR. 4. 4. Afterdischarge-like responses and decreased sound-induced inhibition are observed in neurophysiological recordings from neurons of the inferior colliculus (IC) in the GEPR. 5. 5. Significant deficits of norepinephrine and serotonin are observed in many regions of the GEPR brain. 6. 6. Increases in the number of GABAergic neurons and a reduced effectiveness of iontophoretically-applied GABA are observed in the IC of this animal. 7. 7. GABA agonists or an excitant amino acid (EAA) antagonist block AGS susceptibility when microinjected into brainstem auditory nuclei of the GEPR up to the level of IC. 8. 8. A GABA antagonist or an EAA agonist induces susceptibility to AGS in normal rats following microinjection into IC. An increase in EAA release in IC during AGS in the GEPR is also observed. 9. 9. This increased release of EAA and the reduced effectiveness of GABA in IC may be important seizure initiation mechanisms in the GEPR. 10. 10. The AGS pathway in the GEPR appears to involve the auditory nuclei up to the IC as well as the brainstem reticular formation and substantia nigra but not the entopenduncular nucleus or hippocampus.