PMID- 28858297
OWN - NLM
STAT- MEDLINE
DCOM- 20180924
LR  - 20221207
IS  - 1745-7254 (Electronic)
IS  - 1671-4083 (Print)
IS  - 1671-4083 (Linking)
VI  - 39
IP  - 1
DP  - 2018 Jan
TI  - YL-0919, a dual 5-HT(1A) partial agonist and SSRI, produces antidepressant- and 
      anxiolytic-like effects in rats subjected to chronic unpredictable stress.
PG  - 12-23
LID - 10.1038/aps.2017.83 [doi]
AB  - YL-0919 has been identified as a novel dual 5-HT(1A) partial agonist and 
      serotonin reuptake inhibitor. In the current study, we demonstrated that YL-0919 
      produced prominent antidepressant-like and anxiolytic-like effects in a chronic 
      unpredictable stress (CUS) rat model. Male SD rats were exposed to CUS for 5 
      weeks; YL-0919 (1.25 and 2.5 mg/kg) or a positive control fluoxetine (Flx, 10 
      mg/kg) was orally administered daily. YL-0919 or Flx treatment significantly 
      increased the sucrose preference rate, the locomotor activity in an open field 
      test (OFT), the latency to feed in a novelty-suppressed feeding test (NSFT), and 
      both the percentage of time spent in the open arms and the number of entries into 
      the open arms in an elevated plus-maze test. YL-0919 or Flx treatment 
      significantly suppressed the serum levels of ACTH and corticosterone in 
      CUS-exposed rats. Additionally, YL-0919 or Flx treatment significantly enhanced 
      the levels of cAMP, the expression of phosphorylated cAMP response 
      element-binding protein (pCREB) and brain-derived neurotrophic factor (BDNF) in 
      the hippocampus of CUS-exposed rats. Similar to Flx, YL-0919 treatment 
      significantly enhanced the dendritic complexity, and increased the number of 
      dendritic nodes as well as the spine length and number of branch nodes in the 
      hippocampal pyramidal neurons of CUS-exposed rats. Overall, our results reveal 
      that YL-0919 suppresses the HPA axis and exerts antidepressant-like and 
      anxiolytic-like effects in CUS-exposed rats, which are associated with the 
      enhanced cAMP signaling and hippocampal dendritic complexity.
FAU - Ran, Yu-Hua
AU  - Ran YH
AD  - Department of New Drug Evaluation, State Key Laboratory of Toxicology Medical 
      Courtermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing 
      100850, China.
FAU - Hu, Xiao-Xu
AU  - Hu XX
AD  - Department of New Drug Evaluation, State Key Laboratory of Toxicology Medical 
      Courtermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing 
      100850, China.
AD  - Zoucheng Senior Vocational Technical School, Jining 273500, China.
FAU - Wang, Yu-Lu
AU  - Wang YL
AD  - Department of New Drug Evaluation, State Key Laboratory of Toxicology Medical 
      Courtermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing 
      100850, China.
AD  - College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou 
      350108, China.
FAU - Zhao, Nan
AU  - Zhao N
AD  - Department of New Drug Evaluation, State Key Laboratory of Toxicology Medical 
      Courtermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing 
      100850, China.
FAU - Zhang, Li-Ming
AU  - Zhang LM
AD  - Department of New Drug Evaluation, State Key Laboratory of Toxicology Medical 
      Courtermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing 
      100850, China.
FAU - Liu, Hua-Xia
AU  - Liu HX
AD  - College of Nursing, Taishan Medical University, Taian 271000, China.
FAU - Li, Yun-Feng
AU  - Li YF
AD  - Department of New Drug Evaluation, State Key Laboratory of Toxicology Medical 
      Courtermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing 
      100850, China.
LA  - eng
PT  - Journal Article
DEP - 20170831
PL  - United States
TA  - Acta Pharmacol Sin
JT  - Acta pharmacologica Sinica
JID - 100956087
RN  - 0 (1-(1-benzyl-4-hydroxypiperidin-4-ylmethyl)-2(1H)-pyridinone)
RN  - 0 (Anti-Anxiety Agents)
RN  - 0 (Antidepressive Agents)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Cyclic AMP Response Element-Binding Protein)
RN  - 0 (Piperidines)
RN  - 0 (Pyridones)
RN  - 0 (Serotonin 5-HT1 Receptor Agonists)
RN  - 0 (Serotonin Uptake Inhibitors)
RN  - 01K63SUP8D (Fluoxetine)
RN  - E0399OZS9N (Cyclic AMP)
SB  - IM
MH  - Animals
MH  - Anti-Anxiety Agents/*therapeutic use
MH  - Antidepressive Agents/*therapeutic use
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - Cyclic AMP/metabolism
MH  - Cyclic AMP Response Element-Binding Protein/metabolism
MH  - Dendrites/metabolism
MH  - Depression/*drug therapy
MH  - Fluoxetine/therapeutic use
MH  - Hippocampus/metabolism
MH  - Male
MH  - Piperidines/*therapeutic use
MH  - Pyramidal Cells/metabolism
MH  - Pyridones/*therapeutic use
MH  - Rats, Sprague-Dawley
MH  - Serotonin 5-HT1 Receptor Agonists/*therapeutic use
MH  - Selective Serotonin Reuptake Inhibitors/*therapeutic use
PMC - PMC5758671
EDAT- 2017/09/01 06:00
MHDA- 2018/09/25 06:00
PMCR- 2019/01/01
CRDT- 2017/09/01 06:00
PHST- 2017/01/08 00:00 [received]
PHST- 2017/04/24 00:00 [accepted]
PHST- 2017/09/01 06:00 [pubmed]
PHST- 2018/09/25 06:00 [medline]
PHST- 2017/09/01 06:00 [entrez]
PHST- 2019/01/01 00:00 [pmc-release]
AID - aps201783 [pii]
AID - 10.1038/aps.2017.83 [doi]
PST - ppublish
SO  - Acta Pharmacol Sin. 2018 Jan;39(1):12-23. doi: 10.1038/aps.2017.83. Epub 2017 Aug 
      31.