Effects of citalopram, a synthetic serotonin uptake inhibitor, on indoleamine and catecholamine concentrations in the cerebrospinal fluid of freely moving rats

  • H. Tohgi
  • T. Abe
  • M. Nakanishi
  • S. Takahashi
  • H. Furuichi
  • T. Matsumura
  • T. Kurimoto
  • J. Izumi
  • Y. Ikeda
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Summary

We studied changes in the concentrations of 5-hydroxytryptamine (5-HT), other indoleamines, and catecholamines in the cerebrospinal fluid (CSF) of freely-moving rats that had been administered citalopram, ±1-[3-(Dimethylamino)propyl)-1-(4-fluorophenyl)-1, 3-dihydro-5-isobenzofurancarbonitrile hydrobromide), a selective inhibitor of 5-HT uptake. In a microdialysis experiment, the intracerebral extracellular free 5-HT increased significantly, peaking 60 to 90 min after citalopram (30 mg/kg p.o.) was administerd. The 5-HT concentrations in CSF from the cisterna magna increased significantly, reaching a maximum 6 hours after a single dose of citalopram (30 mg/kg p.o.) was given. Six hours after this dose, the CSF 5-HT concentration in the cisterna magna was significantly increased, and the 5-hydroxyindoleacetic acid (5-HIAA) concentration was significantly decreased. There were non-significant changes in the other indoleamines (tryptophan, 5-hydroxytryptophan, and kynurenine) and in the catecholamines (dopamine, homovanillic acid, normetanephrine, and 3-methoxy-4-hydroxyphenethyleneglycol). The 5-HT/tryptophan ratio was correlated significantly with the kynurenine/tryptophan ratio before treatment with citalopram (r=0.81, p=0.051), indicative that there is coordination of the serotonin and kynurenine pathways in normal rats. In the animals posttreatment there was no such correlation, suggesting that the changes in 5-HT are independent of the kynurenine system at least within the 6 hours postreatment. These CSF results appear to reflect selective inhibition of 5-HT uptake in brain tissues by citalopram that is not associated with changes in catecholamines.

Keywords

Citalopram serotonin cerebrospinal fluid rat 
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Copyright information

© Springer-Verlag 1995

Authors and Affiliations

  • H. Tohgi
    • 1
  • T. Abe
    • 1
  • M. Nakanishi
    • 1
  • S. Takahashi
    • 1
  • H. Furuichi
    • 2
  • T. Matsumura
    • 2
  • T. Kurimoto
    • 2
  • J. Izumi
    • 2
  • Y. Ikeda
    • 2
  1. 1.Department of NeurologyIwate Medical UniversityMoriokaJapan
  2. 2.Department of Pharmacology, Central Research LaboratoriesZeria Pharmaceutical Co., Ltd.SaitamaJapan

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