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

article Etazolate PDE4 GABA Alpha-secretase Cognition Etazolate is a phosphodiesterase 4 (PDE4) inhibitor and GABAA receptor modulator that also stimulates alpha- secretase activity and neurotrophic soluble amyloid precursor protein (sAPPα) production, currently developed as a possible Alzheimer's disease therapeutic. In this study two doses of etazolate were tested for cognitive effects innormallyaged rats,usingacomplex spatiallearning andmemorytask thatemphasized 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-specifi cd eficit 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. © 2010 Elsevier B.V. All rights reserved.