Changes in monoamine metabolites concentrations in rat cerebrospinal fluid after acute and long-term administration of a selective serotonin reuptake inhibitor, trazodone

T. Egashira, Fusako Takayama, Y. Yamanaka

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In order to clarify the mechanism of the antidepressive effects of trazodone, a selective serotonin reuptake inhibitor, we investigated the dynamics of monoamine metabolites in cerebrospinal fluid (CSF) of free-moving conscious rats by acute and long-term treatment with trazodone. When 100 mg kg-1 p.o. of trazodone were administered, a significant increase of 3-methoxy-4-hydroxyphenylglycol (MHPG) concentration was soon observed in the light period of the light/dark cycle, and a significant decrease of dihydroxy phenyl acetic acid (DOPAC) concentration was observed during the 2 days after administration of trazodone; in contrast, the homovanilic acid (HVA) level was increased. However, we detected no significant changes in the 5-hydroxy indole-3-acetic acid (5-HIAA) concentration during the 3 days. In the case of long-term treatment with 50 mg kg-1, p.o. of trazodone, the levels of MHPG, DOPAC and HVA exhibited no difference when compared with values obtained during saline treatment in either the light or dark period, whereas the levels of 5-HIAA showed a significant increase during the light period. These findings suggest that a long-term treatment with trazodone enhances the serotonergic neurons.

Original languageEnglish
Pages (from-to)503-508
Number of pages6
JournalPharmacological Research
Issue number6
Publication statusPublished - Dec 1999
Externally publishedYes



  • Antidepressant
  • Cerebrospinal fluid
  • Monoamine metabolite
  • Selective serotonin reuptake inhibitors
  • Trazodone

ASJC Scopus subject areas

  • Pharmacology

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