PMID- 36166962
OWN - NLM
STAT- MEDLINE
DCOM- 20221021
LR  - 20221021
IS  - 1950-6007 (Electronic)
IS  - 0753-3322 (Linking)
VI  - 155
DP  - 2022 Nov
TI  - L-4-Fluorophenylglycine produces antidepressant-like effects and enhances 
      resilience to stress in mice.
PG  - 113726
LID - S0753-3322(22)01115-5 [pii]
LID - 10.1016/j.biopha.2022.113726 [doi]
AB  - D-serine has attracted increasing attention for its possible role in depression. 
      L-4-Fluorophenylglycine (L-4FPG), an inhibitor of the neutral amino acid 
      transporter ASCT1/2, has been shown to regulate extracellular D-serine levels. 
      The present study aimed to explore the potential antidepressant effects of 
      L-4FPG. First, the acute effects of L-4FPG on the forced swimming test, elevated 
      plus maze test, and novelty-suppressed feeding test were examined. L-4FPG showed 
      antidepressant-like effects, which could be reversed by rapamycin, a mammalian 
      target of rapamycin (mTOR) inhibitor, and 6-cyano-7-nitroquinoxaline-2,3-dione 
      (CNQX), an alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) 
      receptor antagonist. The phosphorylation levels of mTOR and GluR1 in the 
      hippocampus were also increased after L-4FPG treatment. Next, the therapeutic 
      effects of L-4FPG were examined in a chronic social defeat stress (CSDS) model of 
      depression. L-4FPG ameliorated depression-like behaviors in mice subjected to 
      CSDS. Furthermore, treatment with L-4FPG prior to each social defeat stress 
      session not only decreased defensive behaviors but also prevented CSDS-induced 
      social avoidance and anxiety-like and depression-like behaviors. These findings 
      suggest that L-4FPG may be useful not only in alleviating depression but also in 
      protecting against chronic stress-related psychiatric disorders.
CI  - Copyright (c) 2022 The Authors. Published by Elsevier Masson SAS.. All rights 
      reserved.
FAU - Sung, Che-Wei
AU  - Sung CW
AD  - Institute of Systems Neuroscience, National Tsing-Hua University, 101, Section 2, 
      Kuang-Fu Road, Hsinchu 300044, Taiwan; Center for Neuropsychiatric Research, 
      National Health Research Institutes, 35 Keyan Road, Zhunan, Miaoli County 35053, 
      Taiwan.
FAU - Chang, Wei-Tang
AU  - Chang WT
AD  - Center for Neuropsychiatric Research, National Health Research Institutes, 35 
      Keyan Road, Zhunan, Miaoli County 35053, Taiwan.
FAU - Chan, Ming-Huan
AU  - Chan MH
AD  - Institute of Neuroscience, National Chengchi University, 64, Section 2, Zhinan 
      Road, Taipei 11605, Taiwan.
FAU - Kuo, Tsung-Han
AU  - Kuo TH
AD  - Institute of Systems Neuroscience, National Tsing-Hua University, 101, Section 2, 
      Kuang-Fu Road, Hsinchu 300044, Taiwan. Electronic address: 
      thkuo@life.nthu.edu.tw.
FAU - Chen, Hwei-Hsien
AU  - Chen HH
AD  - Center for Neuropsychiatric Research, National Health Research Institutes, 35 
      Keyan Road, Zhunan, Miaoli County 35053, Taiwan; Institute of Neuroscience, 
      National Chengchi University, 64, Section 2, Zhinan Road, Taipei 11605, Taiwan. 
      Electronic address: hwei@nhri.org.tw.
LA  - eng
PT  - Journal Article
DEP - 20220924
PL  - France
TA  - Biomed Pharmacother
JT  - Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
JID - 8213295
RN  - 6OTE87SCCW (6-Cyano-7-nitroquinoxaline-2,3-dione)
RN  - 93939-74-3 (4-fluorophenylglycine)
RN  - 77521-29-0 (alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid)
RN  - 0 (Antidepressive Agents)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - 452VLY9402 (Serine)
RN  - W36ZG6FT64 (Sirolimus)
RN  - 0 (Amino Acid Transport Systems, Neutral)
SB  - IM
MH  - Mice
MH  - Animals
MH  - 6-Cyano-7-nitroquinoxaline-2,3-dione/metabolism/pharmacology
MH  - *Depression/drug therapy/metabolism
MH  - alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid/pharmacology
MH  - Stress, Psychological/drug therapy/metabolism
MH  - Mice, Inbred C57BL
MH  - Antidepressive Agents/pharmacology
MH  - TOR Serine-Threonine Kinases/metabolism
MH  - Hippocampus
MH  - Serine/metabolism/pharmacology
MH  - Sirolimus/pharmacology
MH  - *Amino Acid Transport Systems, Neutral/metabolism/pharmacology
MH  - Mammals
OTO - NOTNLM
OT  - AMPA receptor
OT  - ASCT
OT  - Anxiety
OT  - Depression
OT  - MTOR
OT  - Social defeat stress
COIS- Declaration of Competing Interest The authors declare no competing financial 
      interests.
EDAT- 2022/09/28 06:00
MHDA- 2022/10/22 06:00
CRDT- 2022/09/27 18:22
PHST- 2022/08/01 00:00 [received]
PHST- 2022/09/13 00:00 [revised]
PHST- 2022/09/19 00:00 [accepted]
PHST- 2022/09/28 06:00 [pubmed]
PHST- 2022/10/22 06:00 [medline]
PHST- 2022/09/27 18:22 [entrez]
AID - S0753-3322(22)01115-5 [pii]
AID - 10.1016/j.biopha.2022.113726 [doi]
PST - ppublish
SO  - Biomed Pharmacother. 2022 Nov;155:113726. doi: 10.1016/j.biopha.2022.113726. Epub 
      2022 Sep 24.