FURTHER EVIDENCE OF ANTICONVULSANT ROLE FOR 5-HYDROXYTRYPTAMINE IN GENETICALLY EPILEPSY-PRONE RATS

1 This study was designed to evaluate further the role of 5-hydroxytry ptamine (5-HT) in regulating susceptibility and/or intensity of audiog enic seizures in genetically epilepsy-prone rats. 2 The effects of ser traline, a highly selective and potent inhibitor of 5-HT uptake, on bo th the intensity of the audiogenic seizures and the extracellular conc entrations of 5-HT in the thalamus were evaluated in severe seizure ge netically epilepsy-prone rats. 3 Sertraline (7.5, 15 and 30 mg kg(-1), i.p.) produced a dose-dependent reduction in the intensity of the aud iogenic seizures. 4 Brain microdialysis studies showed that the same d oses of sertraline also caused dose-dependent increases in the extrace llular 5-HT concentration in the thalamus of the freely moving rats. 5 The peak anticonvulsant effect correlated temporally with the peak in creases in the extracellular 5-HT concentration for this drug. 6 It is concluded that enhancement of 5-hydroxytryptaminergic transmission ma y contribute to the anticonvulsant effect of sertraline in severe seiz ure genetically epilepsy-prone rats. 7 The present results coupled wit h earlier investigations support the hypothesis that 5-HT plays an ant iconvulsant role in genetically epilepsy-prone rats.