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-hydroxytryptamine (5-HT) in regulating susceptibility and/or intensity of audiogenic seizures in genetically epilepsy-prone rats. 2. The effects of sertraline, a highly selective and potent inhibitor of 5-HT uptake, on both the intensity of the audiogenic seizures and the extracellular concentrations of 5-HT in the thalamus were evaluated in severe seizure genetically 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 audiogenic seizures. 4. Brain microdialysis studies showed that the same doses of sertraline also caused dose-dependent increases in the extracellular 5-HT concentration in the thalamus of the freely moving rats. 5. The peak anticonvulsant effect correlated temporally with the peak increases in the extracellular 5-HT concentration for this drug. 6. It is concluded that enhancement of 5-hydroxytryptaminergic transmission may contribute to the anticonvulsant effect of sertraline in severe seizure genetically epilepsy-prone rats. 7. The present results coupled with earlier investigations support the hypothesis that 5-HT plays an anticonvulsant role in genetically epilepsy-prone rats.