Selective inhibition of phosphodiesterase 5 enhances glutamatergic synaptic plasticity and memory in mice
Article first published online: 3 JUN 2013
Copyright © 2013 Wiley Periodicals, Inc.
Volume 67, Issue 11, pages 741–747, November 2013
How to Cite
Uthayathas, S., Parameshwaran, K., Karuppagounder, S. S., Ahuja, M., Dhanasekaran, M. and Suppiramaniam, V. (2013), Selective inhibition of phosphodiesterase 5 enhances glutamatergic synaptic plasticity and memory in mice. Synapse, 67: 741–747. doi: 10.1002/syn.21676
- Issue published online: 17 SEP 2013
- Article first published online: 3 JUN 2013
- Accepted manuscript online: 26 APR 2013 02:50AM EST
- Manuscript Accepted: 11 APR 2013
- Manuscript Received: 20 JAN 2013
- Alzheimer's Association. Grant Number: NIRG-08-91816
- synaptic plasticity;
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.