Anticonvulsant effect of enhancement of noradrenergic transmission in the superior colliculus in genetically epilepsy-prone rats (GEPRs): a microinjection study

Abstract

An expanding body of data has indicated that the seizure prone state in genetically epilepsy-prone rats (GEPRs) is partially caused by deficits in central nervous system noradrenergic transmission. Several lines of evidence suggest that the noradrenergic terminals in the superior colliculus (SC) may act as determinants of seizure predisposition in the GEPR. In order to assess the role of the noradrenergic transmission in the SC in the regulation of seizure severity, several drugs with different mechanisms of enhancing noradrenergic transmission were bilaterally microinfused into the SC of GEPR-9s (severe seizure GEPRs). The rats were tested for audiogenic seizure intensity at 0.25, 1, 2, 3, and 4 h after treatments. Bilateral infusion of vehicle produced no reduction in the severity of the audiogenic seizure. Desipramine (2, 4, 8 micrograms/side), nisoxetine (2, 4, 8 micrograms/side), and idazoxan (0.25, 1, 4 micrograms/side) all decreased the seizure severity in a dose-dependent fashion. Significant decreases in the seizure severity were also observed after administration of methoxamine (0.15 microgram/side) or phenylephrine (0.15 microgram/side). Pretreatment with prazosin (1 microgram/side) significantly diminished the anticonvulsant effectiveness of methoxamine and nisoxetine while prazosin, by itself, had no effects on the seizure intensity. These results suggest that noradrenergic transmission in the SC may be involved in the seizure regulation in GEPR-9s, and that this regulation may be mediated, at least in part, through alpha 1 receptors.