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

被引：42

作者：

Drott, Jason ^{[2
]}

Desire, L. ^{[1
]}

Drouin, D. ^{[1
]}

Pando, M. ^{[3
]}

Haun, Forrest ^{[2
]}

机构：

[1] ExonHit Therapeut, F-75013 Paris, France

[2] NeuroDetect Int, Wyncote, PA 19095 USA

[3] ExonHit Therapeut Inc, Gaithersburg, MD 20877 USA

来源：

EUROPEAN JOURNAL OF PHARMACOLOGY | 2010年 / 634卷 / 1-3期

关键词：

Alzheimer's disease; Etazolate; PDE4; GABA; Alpha-secretase; Cognition; AMYLOID PRECURSOR PROTEIN; FIMBRIA-FORNIX LESIONS; PATH-INTEGRATION; ALPHA; HIPPOCAMPUS; BEHAVIOR; DEFICITS; SENSE;

D O I：

10.1016/j.ejphar.2010.02.036

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

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.

引用

页码：95 / 100

页数：6

共 31 条

[1] Reduced cerebrospinal fluid levels of α-secretase-cleaved amyloid precursor protein in aged rats:: Correlation with spatial memory deficits [J].