Fluoxetine inhibition of glycine receptor activity in rat hippocampal neurons

Zeng You Ye, Yun Gang Lu, Hao Sun, Xin Ping Cheng, Tian Le Xu, Jiang Ning Zhou

Research output: Contribution to journalArticle

Abstract

Fluoxetine is a selective serotonin reuptake inhibitor widely used for treating depression. However, fluoxetine treatment may lead to seizures at higher doses, which underlying mechanism remains largely unknown. In this study, we examined the effects of fluoxetine on glycine receptor (GlyR) activity. Using the whole-cell patch-clamp recording method, we found that fluoxetine and its metabolite norfluoxetine inhibited glycine-induced currents in cultured rat hippocampal neurons. This inhibition was dose-dependent, and voltage-independent. Fluoxetine shifted the glycine concentration-response curve to the right without altering the maximal current. Both Lineweaver-Burk and Schild plots suggest competitive inhibition. The amount of fluoxetine inhibition significantly increased when homomeric GlyRs were selectively inhibited with picrotoxin. Moreover, fluoxetine inhibited the current mediated by heteromeric α2β- but not homomeric α2-GlyRs transiently expressed in HEK293T cells. These results suggest that fluoxetine is a competitive and subtype-selective GlyR inhibitor, which may explain its capacity to induce seizures.

Original languageEnglish (US)
Pages (from-to)77-84
Number of pages8
JournalBrain research
Volume1239
DOIs
StatePublished - Nov 6 2008

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Keywords

  • Antidepressant
  • Competitive inhibition
  • Fluoxetine-associated seizure
  • Hippocampus
  • Subtype-selectivity
  • Whole-cell patch-clamp

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

Cite this

Ye, Z. Y., Lu, Y. G., Sun, H., Cheng, X. P., Xu, T. L., & Zhou, J. N. (2008). Fluoxetine inhibition of glycine receptor activity in rat hippocampal neurons. Brain research, 1239, 77-84. https://doi.org/10.1016/j.brainres.2008.08.055