PMID- 31236807
OWN - NLM
STAT- MEDLINE
DCOM- 20200430
LR  - 20221207
IS  - 1573-7365 (Electronic)
IS  - 0885-7490 (Linking)
VI  - 34
IP  - 5
DP  - 2019 Oct
TI  - The faster-onset antidepressant effects of hypidone hydrochloride (YL-0919).
PG  - 1375-1384
LID - 10.1007/s11011-019-00439-8 [doi]
AB  - Hypidone hydrochloride (YL-0919), is a novel structural antidepressant candidate 
      as a triple selective serotonin re-uptake inhibitor (SSRI), 5-HT(1A) partial 
      agonist and 5-HT(6) agonist. Here, we investigated the rapid onset 
      antidepressant-like effects of YL-0919 and the possible mechanism in rats exposed 
      to a chronic unpredictable stress (CUS) paradigm. In the CUS rats, it was found 
      that fluoxetine (FLX, 10 mg/kg) treatment exerted antidepressant actions on 
      20-22d, while YL-0919 or vilazodone (VLZ, a dual 5-HT(1A) partial agonist and 
      SSRI) administrated once daily exerted faster antidepressant-like behaviors 
      [4 days in the sucrose preference test (SPT) and 6 days in the novelty suppressed 
      feeding test (NSF)]. Thereafter, the serum corticosterone (CORT) and 
      adrenocorticotropic hormone (ACTH) levels were reversed by treatment with YL-0919 
      for 7 days. Furthermore, YL-0919 treatment for 5 days reversed the brain derived 
      neurotrophic factor (BDNF)-mammalian target of rapamycin (mTOR) signaling and the 
      key synaptic proteins, such as post-synaptic density (PSD95), GluR1 and 
      presynaptic protein synapsin1. Meanwhile, the dendritic complexity of pyramidal 
      neurons in prefrontal cortex (PFC) were also increased in the CUS rats. These 
      data suggest that YL-0919 exerts a faster antidepressant-like effect on behaviors 
      and this effect maybe at least partially mediated by the BDNF-mTOR signaling 
      related dendritic complexity increase in the PFC.
FAU - Sun, Li-Jun
AU  - Sun LJ
AD  - Beijing Key Laboratory of Neuropsychopharmacology, State Key Laboratory of 
      Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and 
      Toxicology, 27 Taiping Road, Haidian, Beijing, 100850, China.
FAU - Zhang, Li-Ming
AU  - Zhang LM
AD  - Beijing Key Laboratory of Neuropsychopharmacology, State Key Laboratory of 
      Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and 
      Toxicology, 27 Taiping Road, Haidian, Beijing, 100850, China.
FAU - Liu, Dan
AU  - Liu D
AD  - Central Blood Station of Hengshui, Hengshui, 053000, China.
FAU - Xue, Rui
AU  - Xue R
AD  - Beijing Key Laboratory of Neuropsychopharmacology, State Key Laboratory of 
      Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and 
      Toxicology, 27 Taiping Road, Haidian, Beijing, 100850, China.
FAU - Liu, Yan-Qin
AU  - Liu YQ
AD  - Beijing Key Laboratory of Neuropsychopharmacology, State Key Laboratory of 
      Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and 
      Toxicology, 27 Taiping Road, Haidian, Beijing, 100850, China.
FAU - Li, Lei
AU  - Li L
AD  - Department of Anesthesiology, Beijing Chuiyangliu Hospital, Beijing, 10022, 
      China.
FAU - Guo, Ying
AU  - Guo Y
AD  - Department of Anesthesiology, General Hospital of PLA, Beijing, 100853, China.
FAU - Shang, Chao
AU  - Shang C
AD  - Beijing Key Laboratory of Neuropsychopharmacology, State Key Laboratory of 
      Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and 
      Toxicology, 27 Taiping Road, Haidian, Beijing, 100850, China.
FAU - Yao, Jun-Qi
AU  - Yao JQ
AD  - Beijing Key Laboratory of Neuropsychopharmacology, State Key Laboratory of 
      Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and 
      Toxicology, 27 Taiping Road, Haidian, Beijing, 100850, China.
FAU - Zhang, You-Zhi
AU  - Zhang YZ
AD  - Beijing Key Laboratory of Neuropsychopharmacology, State Key Laboratory of 
      Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and 
      Toxicology, 27 Taiping Road, Haidian, Beijing, 100850, China. zhyouzhi@yahoo.com.
FAU - Li, Yun-Feng
AU  - Li YF
AD  - Beijing Key Laboratory of Neuropsychopharmacology, State Key Laboratory of 
      Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and 
      Toxicology, 27 Taiping Road, Haidian, Beijing, 100850, China. lyf619@aliyun.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190624
PL  - United States
TA  - Metab Brain Dis
JT  - Metabolic brain disease
JID - 8610370
RN  - 0 (1-(1-benzyl-4-hydroxypiperidin-4-ylmethyl)-2(1H)-pyridinone)
RN  - 0 (Antidepressive Agents)
RN  - 0 (Piperidines)
RN  - 0 (Pyridones)
RN  - 0 (Serotonin Uptake Inhibitors)
RN  - 01K63SUP8D (Fluoxetine)
SB  - IM
MH  - Animals
MH  - Antidepressive Agents/pharmacology/*therapeutic use
MH  - Behavior, Animal/*drug effects
MH  - Depression/*drug therapy/metabolism
MH  - Disease Models, Animal
MH  - Eating/*drug effects
MH  - Fluoxetine/pharmacology/therapeutic use
MH  - Male
MH  - Piperidines/pharmacology/*therapeutic use
MH  - Prefrontal Cortex/drug effects/metabolism
MH  - Pyramidal Cells/drug effects/metabolism
MH  - Pyridones/pharmacology/*therapeutic use
MH  - Rats
MH  - Rats, Wistar
MH  - Selective Serotonin Reuptake Inhibitors/pharmacology/therapeutic use
MH  - Stress, Psychological/metabolism
MH  - Time Factors
OTO - NOTNLM
OT  - Antidepressant
OT  - Dendritic complexity
OT  - Faster-onset
OT  - Hypidone hydrochloride
OT  - Prefrontal cortex
EDAT- 2019/06/27 06:00
MHDA- 2020/05/01 06:00
CRDT- 2019/06/26 06:00
PHST- 2019/01/13 00:00 [received]
PHST- 2019/05/20 00:00 [accepted]
PHST- 2019/06/27 06:00 [pubmed]
PHST- 2020/05/01 06:00 [medline]
PHST- 2019/06/26 06:00 [entrez]
AID - 10.1007/s11011-019-00439-8 [pii]
AID - 10.1007/s11011-019-00439-8 [doi]
PST - ppublish
SO  - Metab Brain Dis. 2019 Oct;34(5):1375-1384. doi: 10.1007/s11011-019-00439-8. Epub 
      2019 Jun 24.