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Selective inhibition of phosphodiesterase 5 enhances glutamatergic synaptic plasticity and memory in mice

Authors

  • Subramaniam Uthayathas,

    1. Department of Pharmacal Sciences, Harrison School of Pharmacy, Auburn University, Auburn, Alabama
    2. Department of Pharmacology, Howard University College of Medicine, Washington, DC
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  • Kodeeswaran Parameshwaran,

    1. Department of Pharmacal Sciences, Harrison School of Pharmacy, Auburn University, Auburn, Alabama
    2. Department of Pathobiology, College of Veterinary Medicine, Auburn University, Auburn, Alabama
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  • Senthilkumar S. Karuppagounder,

    1. Department of Pharmacal Sciences, Harrison School of Pharmacy, Auburn University, Auburn, Alabama
    2. Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland
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  • Manuj Ahuja,

    1. Department of Pharmacal Sciences, Harrison School of Pharmacy, Auburn University, Auburn, Alabama
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  • Muralikrishnan Dhanasekaran,

    Corresponding author
    1. Department of Pharmacal Sciences, Harrison School of Pharmacy, Auburn University, Auburn, Alabama
    • Correspondence to: Vishnu Suppiramaniam, Department of Pharmacal Sciences, Harrison School of Pharmacy, Auburn University, Auburn, Alabama. E-mail: suppivd@auburn.edu (or)

      Muralikrishnan Dhanasekaran, Department of Pharmacal Sciences, Harrison School of Pharmacy, Auburn University, Auburn, Alabama. E-mail: dhanamu@auburn.edu

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  • Vishnu Suppiramaniam

    Corresponding author
    1. Department of Pharmacal Sciences, Harrison School of Pharmacy, Auburn University, Auburn, Alabama
    • Correspondence to: Vishnu Suppiramaniam, Department of Pharmacal Sciences, Harrison School of Pharmacy, Auburn University, Auburn, Alabama. E-mail: suppivd@auburn.edu (or)

      Muralikrishnan Dhanasekaran, Department of Pharmacal Sciences, Harrison School of Pharmacy, Auburn University, Auburn, Alabama. E-mail: dhanamu@auburn.edu

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ABSTRACT

Phosphodiesterases (PDEs) belong to a family of proteins that control metabolism of cyclic nucleotides. Targeting PDE5, for enhancing cellular function, is one of the therapeutic strategies for male erectile dysfunction. We have investigated whether in vivo inhibition of PDE5, which is expressed in several brain regions, will enhance memory and synaptic transmission in the hippocampus of healthy mice. We have found that acute administration of sildenafil, a specific PDE5 inhibitor, enhanced hippocampus-dependent memory tasks. To elucidate the underlying mechanism in the memory enhancement, effects of sildenafil on long-term potentiation (LTP) were measured. The level of LTP was significantly elevated, with concomitant increases in basal synaptic transmission, in mice treated with sildenafil (1 mg/kg/day) for 15 days compared to control mice. These results suggest that moderate PDE5 inhibition enhances memory by increasing synaptic plasticity and transmission in the hippocampus. Synapse 67:741–747, 2013. © 2013 Wiley Periodicals, Inc.

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