Centrally administered apelin-13 induces depression-like behavior in mice

Apelin, a novel bioactive peptide highly concentrated in the brain, is identified as the endogenous ligand for angiotensin-like 1 receptor (APJ). The present study was designed to investigate the effect of apelin-13 on emotion-related behavior using the forced swimming test (FST) and tail suspension test (TST). Intracerebroventricular (i.c.v.) administration of apelin-13 (0.3, 1 and 3 mu g/mouse) dose-dependently increased the immobility time in the FST and TST, compared with control group. However, the APJ receptor antagonist apelin-13(F13A) (0.3-10 mu g/mouse, i.c.v.) had no influence on immobility time in the FST. The increase of immobility time induced by apelin-13 was significantly blocked by apelin-13(F13A), nonselective opioid receptor antagonist naloxone and kappa-opioid receptor antagonist nor-binaltorphimine dihydrochloride (nor-BNI), respectively, but not the non-selective corticotrophin-releasing factor (CRF) receptor antagonist alpha-helical CRF9-41 in the FST. In order to eliminate the possibility of a false-positive result in the FST or TST, spontaneous activity and motor function were checked. The results demonstrate that apelin-13 alone or antagonists co-administered with apelin-13 did influence spontaneous activity counts. And apelin-13 had no effect on the motor behavior in the rotarod test and wire hanging test. These results indicate that centrally administered apelin-13 elicited depression-like behavior in mice, which was mediated via APJ receptor and kappa-opioid receptor, but not CRF receptor. (C) 2012 Elsevier Inc. All rights reserved.