Pharmacological inhibition of Phosphodiesterase 7 enhances consolidation processes of spatial memory.

Pharmacological inhibition of Phosphodiesterase 7 enhances consolidation processes of spatial memory. Neurobiol Learn Mem. 2020 Dec 02;:107357 Authors: McQuown S, Paes D, Baumgärtel K, Prickaerts J, Peters M 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 hours 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 hours 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 o...
Source: Neurobiology of Learning and Memory - Category: Neurology Authors: Tags: Neurobiol Learn Mem Source Type: research