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

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

    Research output: Contribution to journalArticleAcademicpeer-review

    251 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 - 2004

    Keywords

    • long-term potentiation
    • dependent protein-kinase
    • soluble guanylyl cyclase
    • cyclic-nucleotide phosphodiesterase
    • messenger nitric-oxide
    • rat-brain
    • retrograde messenger
    • adenosine-deaminase
    • serotonin receptor
    • nmda receptors

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