European Journal of Pharmacology 2010-05-25

Etazolate improves performance in a foraging and homing task in aged rats.

Jason Drott, L Desire, D Drouin, M Pando, Forrest Haun

Index: Eur. J. Pharmacol. 634(1-3) , 95-100, (2010)

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Abstract

Etazolate is a phosphodiesterase 4 (PDE4) inhibitor and GABAA receptor modulator that also stimulates alpha-secretase activity and neurotrophic soluble amyloid precursor protein (sAPPalpha) production, currently developed as a possible Alzheimer's disease therapeutic. In this study two doses of etazolate were tested for cognitive effects in normally aged rats, using a complex spatial learning and memory task that emphasized two naturally occurring behaviors in rodents, foraging for food and returning large pieces of found food to a safe home location. Both etazolate doses completely prevented both (1) a foraging deficit that developed in untreated aged rats over the course of the test, as well as (2) a trial-specific deficit in memory for previously visited food locations that also developed over the course of the test in untreated aged rats. Both doses also significantly reduced a separate memory deficit for changing locations of the animals' home box, plus completely prevented a significant tendency for untreated aged animals to attempt entry into similar-appearing but incorrect home boxes. The combined behavioral data demonstrate positive effects of etazolate on separate age-related cognitive deficits, using a complex task based on naturally occurring rodent behaviors.Copyright 2010 Elsevier B.V. All rights reserved.