Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 350, Issue 2, pp 149–152

Role of serotonin in the anticonvulsant effect of fluoxetine in genetically epilepsy-prone rats

Authors

  • Qing-Shan Yan
    • Department of Basic SciencesUniversity of Illinois College of Medicine at Peoria
  • Phillip C. Jobe
    • Department of Basic SciencesUniversity of Illinois College of Medicine at Peoria
  • Jae Hoon Cheong
    • College of PharmacySeoul National University, Center for Biofunctional Molecules
  • Kwang Ho Ko
    • College of PharmacySeoul National University, Center for Biofunctional Molecules
  • John W. Dailey
    • Department of Basic SciencesUniversity of Illinois College of Medicine at Peoria
Article

DOI: 10.1007/BF00241089

Cite this article as:
Yan, Q., Jobe, P.C., Cheong, J.H. et al. Naunyn-Schmiedeberg's Arch Pharmacol (1994) 350: 149. doi:10.1007/BF00241089

Abstract

This study was designed to demonstrate a role of serotonin in the anticonvulsant effect of fluoxetine, a serotonin reuptake inhibitor, in genetically epilepsy-prone rats. When varied doses of 5-hydroxytryptophan (12.5, 25, 50 mg/kg) were administered i.p. along with a fixed dose of fluoxetine (15 mg/kg) to severe seizure genetically epilepsy-prone rats, the severity of audiogenic seizures was decreased dose-dependently, and the combination treatment also produced a marked potentiation of the anticonvulsant effect when compared with administration of either drug alone. Pretreatment of severe seizure genetically epilepsy-prone rats with p-chlorophenylalanine depleted brain serotonin and reduced the anticonvulsant effectiveness of fluoxetine. By using intracerebral microdialysis, the depletion of serotonin after p-chlorophenylalanine treatment was confirmed by measuring thalamic extracellular serotonin and 5-hydroxyindoleacetic acid concentrations during basal release and in response to a challenge dose of fluoxetine. We concluded that serotonergic transmission may be involved in the anticonvulsant effect of fluoxetine in severe seizure genetically epilepsy-prone rats.

Key words

5-HydroxytryptophanFluoxetinep-chlorophenylalanineSerotoninAnticonvulsant effectDialysisGenetically epilepsy-prone rats

Copyright information

© Springer-Verlag 1994