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

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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., ... 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
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. / Inhibition of phosphodiesterase 2 increases nuronal cGMP, synaptic plasticity and memory performance. In: Neuropharmacology. 2004 ; Vol. 47, No. 7. pp. 1081-1092.
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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.",
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Boess, FG, Hendrix, M, van der Staay, FJ, Erb, C, Schreiber, R, van Staveren, WCG, de Vente, J, Prickaerts, J, Blokland, A & Koenig, G 2004, 'Inhibition of phosphodiesterase 2 increases nuronal cGMP, synaptic plasticity and memory performance', Neuropharmacology, vol. 47, no. 7, pp. 1081-1092. https://doi.org/10.1016/j.neuropharm.2004.07.040

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

In: Neuropharmacology, Vol. 47, No. 7, 01.01.2004, p. 1081-1092.

Research output: Contribution to journalArticleAcademicpeer-review

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Boess FG, Hendrix M, van der Staay FJ, Erb C, Schreiber R, van Staveren WCG et al. Inhibition of phosphodiesterase 2 increases nuronal cGMP, synaptic plasticity and memory performance. Neuropharmacology. 2004 Jan 1;47(7):1081-1092. https://doi.org/10.1016/j.neuropharm.2004.07.040