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

Etazolate is a phosphodiesterase 4 (PDE4) inhibitor and GABA(A) receptor modulator that also stimulates alpha-secretase activity and neurotrophic soluble amyloid precursor protein (sAPP alpha) 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. (C) 2010 Elsevier B.V. All rights reserved.