PMID- 25644419
OWN - NLM
STAT- MEDLINE
DCOM- 20151215
LR  - 20221207
IS  - 1873-7544 (Electronic)
IS  - 0306-4522 (Linking)
VI  - 290
DP  - 2015 Apr 2
TI  - Novel antidepressant candidate RO-05 modulated glucocorticoid receptors 
      activation and FKBP5 expression in chronic mild stress model in rats.
PG  - 255-65
LID - S0306-4522(15)00099-8 [pii]
LID - 10.1016/j.neuroscience.2015.01.044 [doi]
AB  - In this study, a novel TRI (triple reuptake inhibitors) antidepressant candidate 
      RO-05 (4-[1-[1-(benzoyloxy)cyclohexyl]-2-(dimethylamino)ethyl]-phenyl benzoate) 
      was investigated in TST (tail suspension test), FST (forced swimming test) and 
      CMS (chronic mild stress) model. Results showed RO-05 significantly decreased the 
      immobility time in FST and TST at 4.5-, 9-, 18-mg/kg in rats and 9-, 18-, 
      36-mg/kg in mice. Chronic administration of 18-mg/kg RO-05 improved the 
      behavioral index, anhedonia and normalized the hyperactivity of HPA 
      (hypothalamic-pituitary-adrenal axis) of CMS rats. We further investigated the 
      possible mechanisms of RO-05 in the CMS model. Eighteen milligrams per kilogram 
      of RO-05 chronic administration significantly reversed the increase of mRNA and 
      protein expression of FKBP5 in the CMS rat hippocampus, which facilitated the 
      activation of GR- (glucocorticoid receptor) and GR-responsive gene Foxo1 
      expression. RO-05 also elevated the expression of BDNF (brain-derived 
      neurotrophic factor) in CMS rat hippocampus. In summary, our results indicated 
      that RO-05 is a promising antidepressant candidate. The possible antidepressant 
      mechanisms of RO-05 were the modulation of FKBP5 expression, GR activation, 
      corresponding inhibition of HPA axis hyperactivity, and the increase of BDNF 
      expression.
CI  - Copyright (c) 2015 IBRO. Published by Elsevier Ltd. All rights reserved.
FAU - Xing, Y
AU  - Xing Y
AD  - School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, 
      Shenyang, Liaoning 110016, PR China.
FAU - Hou, J
AU  - Hou J
AD  - School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, 
      Shenyang, Liaoning 110016, PR China.
FAU - Meng, Q
AU  - Meng Q
AD  - School of Pharmacy, Yantai University & State Key Laboratory of Long Acting and 
      Targetin Drug Delivery Technologies, Yantai, Shandong 264003, PR China.
FAU - Yang, M
AU  - Yang M
AD  - Shandong Luye Pharmaceutical Co. Ltd., Yantai, Shandong 264003, PR China.
FAU - Kurihara, H
AU  - Kurihara H
AD  - School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, 
      Shenyang, Liaoning 110016, PR China. Electronic address: 
      kurihara_hiroshi@163.com.
FAU - Tian, J
AU  - Tian J
AD  - School of Pharmacy, Yantai University & State Key Laboratory of Long Acting and 
      Targetin Drug Delivery Technologies, Yantai, Shandong 264003, PR China. 
      Electronic address: tianjingwei@luye.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150130
PL  - United States
TA  - Neuroscience
JT  - Neuroscience
JID - 7605074
RN  - 0 (Antidepressive Agents)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Forkhead Transcription Factors)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Neurotransmitter Uptake Inhibitors)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Glucocorticoid)
RN  - 0 (Foxo1 protein, rat)
RN  - EC 5.2.1.- (Tacrolimus Binding Proteins)
RN  - EC 5.2.1.8 (tacrolimus binding protein 5)
SB  - IM
MH  - Animals
MH  - Antidepressive Agents/chemistry/*pharmacology
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - Chronic Disease
MH  - Depressive Disorder/*drug therapy/*metabolism
MH  - Disease Models, Animal
MH  - Dose-Response Relationship, Drug
MH  - Forkhead Transcription Factors/metabolism
MH  - Hippocampus/drug effects/metabolism
MH  - Male
MH  - Mice
MH  - Molecular Structure
MH  - Nerve Tissue Proteins/metabolism
MH  - Neurotransmitter Uptake Inhibitors/chemistry/*pharmacology
MH  - RNA, Messenger/metabolism
MH  - Random Allocation
MH  - Rats, Sprague-Dawley
MH  - Receptors, Glucocorticoid/*metabolism
MH  - Stress, Psychological/drug therapy/metabolism
MH  - Tacrolimus Binding Proteins/*metabolism
OTO - NOTNLM
OT  - FKBP5
OT  - chronic mild stress
OT  - depression
OT  - glucocorticoid receptors
EDAT- 2015/02/04 06:00
MHDA- 2015/12/17 06:00
CRDT- 2015/02/04 06:00
PHST- 2014/09/18 00:00 [received]
PHST- 2015/01/04 00:00 [revised]
PHST- 2015/01/06 00:00 [accepted]
PHST- 2015/02/04 06:00 [entrez]
PHST- 2015/02/04 06:00 [pubmed]
PHST- 2015/12/17 06:00 [medline]
AID - S0306-4522(15)00099-8 [pii]
AID - 10.1016/j.neuroscience.2015.01.044 [doi]
PST - ppublish
SO  - Neuroscience. 2015 Apr 2;290:255-65. doi: 10.1016/j.neuroscience.2015.01.044. 
      Epub 2015 Jan 30.