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 3μg/mouse) dose-dependently increased the immobility time in the FST and TST, compared with control group. However, the APJ receptor antagonist apelin-13(F13A) (0.3-10μg/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), non-selective opioid receptor antagonist naloxone and κ-opioid receptor antagonist nor-binaltorphimine dihydrochloride (nor-BNI), respectively, but not the non-selective corticotrophin-releasing factor (CRF) receptor antagonist α-helical CRF(9-41) 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 κ-opioid receptor, but not CRF receptor.
Institute of Biochemistry and Molecular Biology, School of Life Sciences, Lanzhou University, 222 Tianshui South Road, Lanzhou, Gansu 730000, China. lvshy08@lzu.edu.cn
Shuang-Yu
SY
Lv
Yao-Jun
YJ
Qin
Hai-Ting
HT
Wang
Ning
N
Xu
Yan-Jie
YJ
Yang
Qiang
Q
Chen
D000595:Amino Acid Sequence; D000818:Animals; D000075244:Apelin Receptors; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology; D003863:Depression / Q000139:chemically induced*; D007267:Injections; D007276:Injections, Intraventricular; D036341:Intercellular Signaling Peptides and Proteins / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009270:Naloxone / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D044140:Receptor, Angiotensin, Type 1 / Q000819:agonists* / Q000502:physiology; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors; D043562:Receptors, G-Protein-Coupled / Q000819:agonists* / Q000502:physiology; D017473:Receptors, Opioid, kappa / Q000037:antagonists & inhibitors / Q000502:physiology*; D045442:Rotarod Performance Test; D016037:Single-Blind Method
D000075244:Apelin Receptors; C491285:Aplnr protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D010446:Peptide Fragments; D044140:Receptor, Angiotensin, Type 1; D018019:Receptors, Corticotropin-Releasing Hormone; D043562:Receptors, G-Protein-Coupled; D017473:Receptors, Opioid, kappa; C495199:apelin-13 peptide; C532492:apelin-13, Ala(13)-; D009270:Naloxone; C051844:norbinaltorphimine; D009271:Naltrexone; D003346:Corticotropin-Releasing Hormone; C045089:corticotropin releasing hormone (9-41)