Neither intranigral fluoxetine nor 5,7-dihydroxytryptamine alter audiogenic seizures in genetically epilepsy-prone rats

Previous studies have shown that widespread depletion of brain 5-hydroxytryptamine (5-HT, serotonin) exacerbates audiogenic seizures in genetically epilepsy-prone rats (GEPRs), while elevations in brain 5-HT attenuate these seizures. However, the location of the central nervous system site(s) at which 5-HT exerts its anticonvulsant action on audiogenic seizures, remains unknown. The substantia nigra has been shown to exert modulatory actions over both brainstem and forebrain driven seizures in normal rats, and receives a rich serotonergic innervation. The present study was designed to determine if 5-HT exerts its modulatory effect on audiogenic seizures by an action in the substantia nigra. Microinfusion of 5,7-dihydroxytryptamine (4 mu g/0.25 mu l bilateral) into the substantia nigra of GEPRs which display a moderate seizure (GEPR-3s) failed to alter the audiogenic seizure, Consistent with these findings, microinfusions of fluoxetine-HCl into the substantia nigra of severe seizure GEPRs (GEPR-9s) failed to alter any aspect of the audiogenic seizure. This effect was observed when fluoxetine was infused alone, or in combination with systemic administration of 5-hydroxytryptophan (75 mg/kg, i,p.). The present findings argue against a modulatory role of nigral 5-HT on audiogenic seizures in GEPRs.