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

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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.

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Authors and Affiliations

  1. Department of Basic Sciences, University of Illinois College of Medicine at Peoria, P.O. Box 1649, 61656, Peoria, IL, USA

    Qing-Shan Yan, Phillip C. Jobe & John W. Dailey

  2. College of Pharmacy, Seoul National University, Center for Biofunctional Molecules, Postech, Korea

    Jae Hoon Cheong & Kwang Ho Ko

Authors
  1. Qing-Shan Yan
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  2. Phillip C. Jobe
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  3. Jae Hoon Cheong
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  4. Kwang Ho Ko
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  5. John W. Dailey
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Additional information

Correspondence to: Q. S. Yan at the above address

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Yan, QS., Jobe, P.C., Cheong, J.H. et al. Role of serotonin in the anticonvulsant effect of fluoxetine in genetically epilepsy-prone rats. Naunyn-Schmiedeberg's Arch Pharmacol 350, 149–152 (1994). https://doi.org/10.1007/BF00241089

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  • DOI: https://doi.org/10.1007/BF00241089

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