Caffeic Acid Phenethyl Ester Ameliorates Depression- and Anxiety-like Be- haviors of Mice Exposed to Chronic Mild Stress

Depression and anxiety like symptoms appeared in mice when they were kept in cages and sequentially subjected to leaning, drenching, and rotation within 1-2 days for 3 weeks (chronic mild stress: CMS). The depression-like symptom was evaluated by performing the tail suspension test; and the anxiety-like symptom, by the elevated plus-maze test and light-dark box test. Caffeic Acid Phenethyl Ester (CAPE), a component of propolis, showed a preventive effect against both depressionand anxiety-like symptoms when administered during the stress loading, and CAPE also displayed a therapeutic effect against both symptoms when administered after the stress loading. Furthermore, CAPE restored the CMS-induced decrease in the level of the phosphorylated forms of extracellular signal-regulated protein kinases (ERK) 1/2 and cAMP-response element binding protein (CREB) in the hippocampus to a normal level. These results suggest that CAPE is a promising tool for therapy of mood disorders through activation of the hippocampal ERK1/2-CREB signaling cascade. ©2013 The Authors. Published by the JScholar under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/ by/3.0/, which permits unrestricted use, provided the original author and source are credited.