title: Ghrelin alleviates anxiety- and depression-like behaviors induced by chronic unpredictable mild stress in rodents.
abstract: As a regulator of food intake, ghrelin also plays a key role in mood disorders. Previous studies reported that acute ghrelin administration defends against depressive symptoms of chronic stress. However, the effects of long-term ghrelin on rodents under chronic stress hasn't been revealed. In this study, we found chronic peripheral administration of ghrelin (5nmol/kg/day for 2 weeks, i.p.) could alleviate anxiety- and depression-like behaviors induced by chronic unpredictable mild stress (CUMS). The depression-like behaviors were assessed by the forced swimming test (FST), and anxiety-like behaviors were assessed by the open field test (OFT) and the elevated plus maze test (EPM). Meanwhile, we observed that peripheral acylated ghrelin, together with gastral and hippocampal ghrelin prepropeptide mRNA level, were significantly up-regulated in CUMS mice. Besides, the increased protein level of growth hormone secretagogue receptor (GHSR) in hippocampus were also detected. These results suggested that the endogenous ghrelin/GHSR pathway activated by CUMS plays a role in homeostasis. Further results showed that central treatment of ghrelin (10μg/rat/day for 2 weeks, i.c.v.) or GHRP-6 (the agonist of GHSR, 10μg/rat/day for 2 weeks, i.c.v.) significantly alleviated the depression-like behaviors induced by CUMS in FST and sucrose preference test (SPT). Based on these results, we concluded that central GHSR is involved in the antidepressant-like effect of exogenous ghrelin treatment, and ghrelin/GHSR may have the inherent neuromodulatory properties against depressive symptoms.
authors.affiliation: Department of Integrative Medicine and Neurobiology, State Key Lab of Medical Neurobiology, Institutes of Brain Science, Shanghai Medical College, Fudan University, Shanghai 200032, China.
authors.forename: Hui-Jie
authors.initials: HJ
authors.lastname: Huang
authors.affiliation: Department of Integrative Medicine and Neurobiology, State Key Lab of Medical Neurobiology, Institutes of Brain Science, Shanghai Medical College, Fudan University, Shanghai 200032, China.
authors.forename: Xiao-Cang
authors.initials: XC
authors.lastname: Zhu
authors.affiliation: Department of Integrative Medicine and Neurobiology, State Key Lab of Medical Neurobiology, Institutes of Brain Science, Shanghai Medical College, Fudan University, Shanghai 200032, China.
authors.forename: Qiu-Qin
authors.initials: QQ
authors.lastname: Han
authors.affiliation: Department of Integrative Medicine and Neurobiology, State Key Lab of Medical Neurobiology, Institutes of Brain Science, Shanghai Medical College, Fudan University, Shanghai 200032, China.
authors.forename: Ya-Lin
authors.initials: YL
authors.lastname: Wang
authors.affiliation: Department of Integrative Medicine and Neurobiology, State Key Lab of Medical Neurobiology, Institutes of Brain Science, Shanghai Medical College, Fudan University, Shanghai 200032, China.
authors.forename: Na
authors.initials: N
authors.lastname: Yue
authors.affiliation: Department of Integrative Medicine and Neurobiology, State Key Lab of Medical Neurobiology, Institutes of Brain Science, Shanghai Medical College, Fudan University, Shanghai 200032, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Integrative Medicine and Neurobiology, State Key Lab of Medical Neurobiology, Institutes of Brain Science, Shanghai Medical College, Fudan University, Shanghai 200032, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Yu
authors.affiliation: Center Laboratory, Jinshan Hospital of Fudan University, Shanghai 201508, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Li
authors.affiliation: Department of Integrative Medicine and Neurobiology, State Key Lab of Medical Neurobiology, Institutes of Brain Science, Shanghai Medical College, Fudan University, Shanghai 200032, China.
authors.forename: Gen-Cheng
authors.initials: GC
authors.lastname: Wu
authors.affiliation: Department of Anatomy, Histology and Embryology, Shanghai Medical College, Fudan University, Shanghai, China; Key Laboratory of Medical Imaging Computing and Computer Assisted Intervention of Shanghai, Shanghai 200032, China. Electronic address: liuqiong@fudan.edu.cn.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Integrative Medicine and Neurobiology, State Key Lab of Medical Neurobiology, Institutes of Brain Science, Shanghai Medical College, Fudan University, Shanghai 200032, China. Electronic address: yujin@shmu.edu.cn.
authors.forename: Jin
authors.initials: J
authors.lastname: Yu
mesh_terms: D000818:Animals; D001007:Anxiety / Q000188:drug therapy* / Q000209:etiology; D001522:Behavior, Animal / Q000187:drug effects; D003863:Depression / Q000188:drug therapy* / Q000209:etiology; D054439:Ghrelin / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology*; D006624:Hippocampus / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009842:Oligopeptides / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D054440:Receptors, Ghrelin / Q000819:agonists / Q000378:metabolism*; D013315:Stress, Psychological / Q000150:complications / Q000378:metabolism*
chemical_list: D054439:Ghrelin; D009842:Oligopeptides; D054440:Receptors, Ghrelin; C041048:growth hormone releasing hexapeptide
keywords: CUMS; Depression; Depression-like behaviors; GHSR; Ghrelin