Genetically epilepsy-prone rats (GEPRs) which display tonic seizures (GEPR-9s) in response to acoustic stimulation were used in these studies. Other laboratories have shown that GEPR-9s have a reduced concentration of brain norepinephrine (NE). Previous reports have also indicated that audiogenic seizures (AGS) in these animals are inhibited by treatments that enhance noradrenergic (NA) neurotransmission. AGS in GEPRs are believed to be initiated in the inferior colliculus (IC) where GABA has been shown to exert inhibitory influences in GEPRs that display submaximal AGS. The present study examined whether the IC is a crucial site for NA suppression of tonic seizures by examining the effect of microinfusing NA agonists into the IC. The intracollicular effect of a GABA agonist, muscimol, on sound-induced tonic convulsions in GEPR-9s was also examined. Bilateral microinfusion of NE, phenylephrine, clonidine or isoproterenol failed to alter the AGS. In contrast, muscimol (30 or 60 ng/side) infused into the IC abolished the tonic and clonic components of the AGS in GEPR-9s. These findings suggest that enhancement of GABAergic neurotransmission in the IC markedly attenuates AGS in the GEPR, while augmentation of NA neurotransmission has little effect in this brain region.

Acoustic Stimulation↗

PubMedDate not supplied

Induction of audiogenic seizures in normal and genetically epilepsy-prone rats following focal microinjection of an excitant amino acid into reticular formation and auditory nuclei.

An excitant amino acid (EAA), N-methyl-D-aspartate (NMDA), induces susceptibility to seizures when bilaterally microinjected into subcortical auditory nuclei of normal rats. Thirty-five percent of animals exhibit only audiogenic seizures (AGS) after infusions of NMDA into inferior colliculus (IC). Infusions into cochlear nucleus and medial geniculate body never produce susceptibility to AGS without non-audiogenic seizures (N-AGS). The overall seizure incidence (AGS and N-AGS) with IC infusions is 100%, but the incidence is less than 50% with infusions into cochlear nucleus or medial geniculate body. Although AGS susceptibility is induced by NMDA infusions in normal animals, the seizures are submaximal in severity and lack tonic components. Bilateral infusions of NMDA into IC or reticular formation of the substrain of genetically epilepsy-prone rats (GEPRs) that exhibits submaximal AGS (GEPR-3s) do not increase seizure severity. These data along with studies showing increased EAA levels and excitotoxic-like damage in the IC of the GEPR and blockade of AGS with an EAA receptor antagonist or synthesis inhibitor suggest that an EAA in the IC is involved in initiation of AGS in the GEPR. However, EAA action in the GEPR IC is not sufficient to induce the complete spectrum of seizure behaviors, and additional mechanisms may be required for induction of maximal severity audiogenic seizures.

Acoustic Stimulation↗