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

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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.

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Acknowledgements

This study was supported by the National Research Foundation of Korea (NRF) grant funded by the Ministry of Education, Science and Technology (MEST) (2017R1C1B1003822, 2016R1A5A2007009, and 2015R1A2A2A01007838).

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  1. Jee Hyun Yi and JiaBao Zhang contributed equally to this work.

Authors and Affiliations

  1. School of Clinical Sciences, Faculty of Medicine and Dentistry, University of Bristol, Bristol, UK

    Jee Hyun Yi

  2. Department of Oriental Pharmaceutical Science, College of Pharmacy, Kyung Hee University, Seoul, Republic of Korea

    JiaBao Zhang, Sang Yoon Ko, Se Jin Jeon & Jong Hoon Ryu

  3. Department of Medicinal Biotechnology, College of Health Sciences, Dong-A University, Busan, Republic of Korea

    Huiyoung Kwon, Young Choon Lee & Dong Hyun Kim

  4. School of Natural Resources and Environmental Science, Kangwon National University, Chuncheon, Republic of Korea

    Se Jin Park

  5. Department of Herbal Medicinal Pharmacology, College of Herbal Bio-industry, DaeguHaany University, Kyungsan, Republic of Korea

    Jiwook Jung

  6. Department of Neurology, Chonnam National University Medical School, Gwangju, Republic of Korea

    Byung C. Kim

  7. Institute of Convergence Bio-Health, Dong-A University, Busan, Republic of Korea

    Young Choon Lee & Dong Hyun Kim

  8. Department of Life and Nanopharmaceutical Sciences, Kyung Hee University, Seoul, South Korea

    Jong Hoon Ryu

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Correspondence to Dong Hyun Kim or Jong Hoon Ryu.

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The treatment and maintenance of the animals were carried out in accordance with the Animal Care and Use Guidelines Dong-A University and Kyung Hee University, Korea. All of the experimental protocols using animals were approved by the Institutional Animal Care and Use Committee of Dong-A University and Kyung Hee University, Korea.

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Yi, J.H., Zhang, J., Ko, S.Y. et al. Fluoxetine Inhibits Natural Decay of Long-Term Memory via Akt/GSK-3β Signaling. Mol Neurobiol 55, 7453–7462 (2018). https://doi.org/10.1007/s12035-018-0919-x

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