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

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


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
Issue number7
Publication statusPublished - 1 Jan 2004

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