Injections of noradrenergic and GABAergic agonists into the inferior colliculus: effects on audiogenic seizures in genetically epilepsy-prone rats

Abstract

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.