Fluoxetine Inhibits Natural Decay of Long-Term Memory via Akt/GSK-3β Signaling

Jee Hyun Yi, Jia Bao Zhang, Sang Yoon Ko, Huiyoung Kwon, Se Jin Jeon, Se Jin Park, Jiwook Jung, Byung C. Kim, Young Choon Lee, Dong Hyun Kim, Jong Hoon Ryu*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)

8 Citations (Scopus)

Abstract

Understanding the mechanisms underlying the natural decay of long-term memory can help us find means of extending the duration of long-term memory. However, the neurobiological processes involved in the decay of long-term memory are poorly understood. In the present study, we examined the effect of acute and chronic treatment of fluoxetine on natural decay of long-term memory and the possible mechanism. Late administration of fluoxetine prolonged the persistence of long-term memory in mice, as demonstrated by object location recognition and Barnes maze tests. Fluoxetine altered Akt/glycogen synthase kinase-3β (GSK-3β)/β-catenin signaling in the hippocampus. Late short- and long-term pharmacological inhibition of GSK-3β mimicked the effect of fluoxetine on memory persistence. Pharmacological inhibition of Akt blocked the effect of fluoxetine on memory persistence. Finally, late infusion of fluoxetine increased hippocampal long-term potentiation (LTP) and pharmacological inhibition of GSK-3β blocked the natural decline in LTP. These results demonstrate that GSK-3β might be a key molecule in memory decay process, and fluoxetine extends the period of long-term memory maintenance via Akt/GSK-3β signaling.

Original languageEnglish
Pages (from-to)1-10
Number of pages10
JournalMolecular Neurobiology
DOIs
Publication statusE-pub ahead of print - 9 Feb 2018

Keywords

  • Fluoxetine
  • GSK-3β
  • LTP maintenance
  • Memory decay

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    Yi, J. H., Zhang, J. B., Ko, S. Y., Kwon, H., Jeon, S. J., Park, S. J., Jung, J., Kim, B. C., Lee, Y. C., Kim, D. H., & Ryu, J. H. (2018). Fluoxetine Inhibits Natural Decay of Long-Term Memory via Akt/GSK-3β Signaling. Molecular Neurobiology, 1-10. https://doi.org/10.1007/s12035-018-0919-x