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.
Yan
Q S
QS
Department of Basic Sciences, University of Illinois College of Medicine at Peoria 61656, USA.
Jobe
P C
PC
Dailey
J W
JW
D015057:1-Naphthylamine / Q000031:analogs & derivatives / Q000627:therapeutic use; D000161:Acoustic Stimulation; D000818:Animals; D004827:Epilepsy / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology*; D005110:Extracellular Space / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008297:Male; D017551:Microdialysis; D051381:Rats; D012701:Serotonin / Q000378:metabolism / Q000502:physiology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use; D020280:Sertraline; D013788:Thalamus / Q000378:metabolism
D015057:1-Naphthylamine; D006897:Hydroxyindoleacetic Acid; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors; D020280:Sertraline