title: Selective inhibition of phosphodiesterase 5 enhances glutamatergic synaptic plasticity and memory in mice.
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.
authors.affiliation: Department of Pharmacal Sciences, Harrison School of Pharmacy, Auburn University, Auburn, Alabama; Department of Pharmacology, Howard University College of Medicine, Washington, DC.
authors.forename: Subramaniam
authors.initials: S
authors.lastname: Uthayathas
authors.forename: Kodeeswaran
authors.initials: K
authors.lastname: Parameshwaran
authors.forename: Senthilkumar S
authors.initials: SS
authors.lastname: Karuppagounder
authors.forename: Manuj
authors.initials: M
authors.lastname: Ahuja
authors.forename: Muralikrishnan
authors.initials: M
authors.lastname: Dhanasekaran
authors.forename: Vishnu
authors.initials: V
authors.lastname: Suppiramaniam
mesh_terms: D000818:Animals; D019706:Excitatory Postsynaptic Potentials; D006624:Hippocampus / Q000166:cytology / Q000502:physiology; D017774:Long-Term Potentiation / Q000187:drug effects*; D018782:Maze Learning; D008568:Memory / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000502:physiology; D058986:Phosphodiesterase 5 Inhibitors / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology*; D011687:Purines / Q000494:pharmacology; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000494:pharmacology*
chemical_list: D058986:Phosphodiesterase 5 Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D000068677:Sildenafil Citrate
keywords: hippocampus; memory; phosphodiesterases; sildenafil; synaptic plasticity