Effects of fluoxetine on basal and K+-induced tritium release from synaptosomes preloaded with [3H]serotonin

M. Gobbi, D. Crespi, T. Mennini

Research output: Contribution to journalArticlepeer-review

Abstract

Synaptosomes from rat brain cortex and spinal cord were preloaded with [3H]serotonin (3H]5-HT), super/fused and exposed to fluoxetine and/or 15 mM K+. In both regions 10 μM, but not 1 μM fluoxetine evoked a marked tritium overflow, about 2 min later than the immediate [3H]5-HT release induced by K+, and mainly (73%) due to the efflux of a tritiated metabolite of 5-HT, possibly [3H]5-hydroxy-indoleacetic acid. These findings confirm previous data in the rat hippocampus and are probably due to fluoxetine interacting with the 5-HT storage vesicles. One μM fluoxetine significantly reduced the d-fenfluramine-induced [3H]5-HT overflow, in accordance with its action as 5-HT uptake blocker, but did not affect the K+-induced [3H]5-HT overflow. This latter finding does not confirm that fluoxetine inhibits the depolarization-induced Ca2+-influx, suggested to involve a drug interaction with the L-type Ca2+-channels. Thus, the overflow induced by 10 μM fluoxetine was additive with the depolarization-induced overflow, when the two stimuli were applied together. When 10 μM fluoxetine was added 7 min before 15 mM K+, there was no depolarization-induced overflow. Such inhibition might be only apparent and due either to the fluoxetine-induced loss of vesicular 5-HT or to a fluoxetine-induced alteration of synaptic vesicles. The in vivo relevance of the fluoxetine releasing effect remains to be assessed.

Original languageEnglish
Pages (from-to)785-791
Number of pages7
JournalLife Sciences
Volume56
Issue number10
DOIs
Publication statusPublished - Jan 27 1995

Keywords

  • fluoxetine
  • serotonin release
  • synaptosomes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Pharmacology

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