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Updated: May 3, 2026

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Cilostazol improves hippocampus-dependent long-term memory in mice.

Shuichi Yanai1, Yuki Semba, Hideki Ito

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The phosphodiesterase 3 (PDE3) inhibitor cilostazol enhances hippocampus-dependent long-term memory and boosts cAMP signaling in mice. This suggests potential cognitive benefits for learning and memory.

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Area of Science:

  • Neuroscience
  • Pharmacology

Background:

  • Phosphodiesterases (PDEs) regulate cyclic adenosine monophosphate (cAMP) signaling.
  • PDE inhibitors are explored for cognitive enhancement, but PDE3 inhibitors' effects on memory remain unclear.

Purpose of the Study:

  • To investigate the impact of the PDE3 inhibitor cilostazol on memory function in C57BL/6 J mice.
  • To analyze the effect of cilostazol on cAMP-responsive element binding protein (CREB) phosphorylation in the hippocampus.

Main Methods:

  • Behavioral assessment using Morris water maze and fear conditioning tasks.
  • Immunohistochemical analysis to quantify phosphorylated CREB (pCREB) in the hippocampus.

Main Results:

  • Cilostazol significantly improved spatial memory recall and context-dependent long-term fear memory.
  • No effect on short-term memory or cue-dependent fear memory was observed.
  • Increased pCREB-positive cells in the hippocampal dentate gyrus were noted.

Conclusions:

  • Cilostazol selectively enhances hippocampus-dependent long-term memory.
  • The beneficial effects may stem from enhanced cAMP signaling within the hippocampus.