Inhibition of phosphodiesterase 2 increases nuronal cGMP, synaptic plasticity and memory performance

F G. Boess, M. Hendrix, F.J. van der Staay, C. Erb, R. Schreiber, W.C.G. van Staveren, J. de Vente, J. Prickaerts, A. Blokland, G. Koenig

Research output: Contribution to journalArticleAcademicpeer-review

181 Citations (Scopus)

Abstract

An essential element of the signalling cascade leading to synaptic plasticity is the intracellular second messenger molecule guanosine 3',5'-cyclic monophosphate (cGMP). Using the novel, potent, and selective inhibitor Bay 60-7550, we show that the enzyme 3',5'-cyclic nucleotide phosphodiesterase type 2 (PDE2) is responsible for the degradation of newly synthesized cGMP in cultured neurons and hippocampal slices. Inhibition of PDE2 enhanced long-term potentiation of synaptic transmission without altering basal synaptic transmission. Inhibition of PDE2 also improved the performance of rats in social and object recognition memory tasks, and reversed MK801-induced deficits in spontaneous alternation in mice in a T-maze. Our data provide strong evidence that inhibition of PDE2 can improve memory functions by enhancing neuronal plasticity.
Original languageEnglish
Pages (from-to)1081-1092
JournalNeuropharmacology
Volume47
Issue number7
DOIs
Publication statusPublished - 1 Jan 2004

Cite this

Boess, F. G., Hendrix, M., van der Staay, F. J., Erb, C., Schreiber, R., van Staveren, W. C. G., de Vente, J., Prickaerts, J., Blokland, A., & Koenig, G. (2004). Inhibition of phosphodiesterase 2 increases nuronal cGMP, synaptic plasticity and memory performance. Neuropharmacology, 47(7), 1081-1092. https://doi.org/10.1016/j.neuropharm.2004.07.040