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Title: | Pharmacological inhibition of phosphodiesterase 7 enhances consolidation processes of spatial memory | Authors: | McQuown, Susan PAES, Dean Baumgartel, Karsten Prickaerts, Jos Peters, Marco |
Issue Date: | 2021 | Publisher: | ACADEMIC PRESS INC ELSEVIER SCIENCE | Source: | NEUROBIOLOGY OF LEARNING AND MEMORY, 177 (Art N° 107357) | Abstract: | Augmentation of cAMP signaling through inhibition of phosphodiesterases (PDE) is known to enhance plasticity and memory. Inhibition of PDE4 enhances consolidation into memory, but less is known about the role of other cAMP specific PDEs. Here, we tested the effects of oral treatment with a selective inhibitor of PDE7 of nanomolar potency on spatial and contextual memory. In an object location task, doses of 0.3-3 mg/kg administered 3 h after training dose-dependently attenuated time-dependent forgetting in rats. Significant enhancement of memory occurred at a dose of 3 mg/kg with corresponding brain levels consistent with PDE7 inhibition. The same dose given prior to training augmented contextual fear conditioning. In mice, daily dosing before training enhanced spatial memory in two different incremental learning paradigms in the Barnes Maze. Drug treated mice made significantly less errors locating the escape in a probe-test 24 h after the end of training, and they exhibited hippocampal-dependent spatial search strategies more frequently than controls, which tended to show serial sampling of escape locations. Acquisition and short-term memory, in contrast, were unaffected. Our data provide evidence for a role of PDE7 in the consolidation of hippocampal-dependent memory. We suggest that targeting PDE7 for memory enhancement may provide an alternative to PDE4 inhibitors, which tend to have undesirable gastrointestinal side-effects. | Notes: | Peters, M (corresponding author), Dart Neurosci LLC, Target Discovery & Behav Pharmacol, 12278 Scripps Summit Dr, San Diego, CA 92131 USA. dr.marco.peters@gmail.com |
Document URI: | http://hdl.handle.net/1942/35736 | ISSN: | 1074-7427 | e-ISSN: | 1095-9564 | DOI: | 10.1016/j.nlm.2020.107357 | ISI #: | WOS:000694866100014 | Category: | A1 | Type: | Journal Contribution | Validations: | ecoom 2022 |
Appears in Collections: | Research publications |
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1-s2.0-S107474272030201X-main.pdf Restricted Access | Published version | 3.19 MB | Adobe PDF | View/Open Request a copy |
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