PMID- 28748374
OWN - NLM
STAT- MEDLINE
DCOM- 20180514
LR  - 20181202
IS  - 1432-2072 (Electronic)
IS  - 0033-3158 (Linking)
VI  - 234
IP  - 21
DP  - 2017 Nov
TI  - Alterations in amino acid levels in mouse brain regions after adjunctive 
      treatment of brexpiprazole with fluoxetine: comparison with (R)-ketamine.
PG  - 3165-3173
LID - 10.1007/s00213-017-4700-z [doi]
AB  - RATIONALE: Brexpiprazole, a serotonin-dopamine activity modulator, is approved in 
      the USA as an adjunctive therapy to antidepressants for treating major depressive 
      disorders. Similar to the N-methyl-D-aspartate receptor (NMDAR) antagonist 
      ketamine, the combination of brexpiprazole and fluoxetine has demonstrated 
      antidepressant-like effects in animal models of depression. OBJECTIVES: The 
      present study was conducted to examine whether the combination of brexpiprazole 
      and fluoxetine could affect the tissue levels of amino acids [glutamate, 
      glutamine, gamma-aminobutyric acid (GABA), D-serine, L-serine, and glycine] that are 
      associated with NMDAR neurotransmission. METHODS: The tissue levels of amino 
      acids in the frontal cortex, striatum, hippocampus, and cerebellum were measured 
      after a single [or repeated (14 days)] oral administration of vehicle, fluoxetine 
      (10 mg/kg), brexpiprazole (0.1 mg/kg), or a combination of the two drugs. 
      Furthermore, we measured the tissue levels of amino acids after a single 
      administration of the NMDAR antagonist (R)-ketamine. RESULTS: A single injection 
      of the combination of fluoxetine and brexpiprazole significantly increased GABA 
      levels in the striatum, the D-serine/L-serine ratio in the frontal cortex, and 
      the glycine/L-serine ratio in the hippocampus. A repeated administration of the 
      combination significantly altered the tissue levels of amino acids in all 
      regions. Interestingly, a repeated administration of the combination 
      significantly decreased the D-serine/L-serine ratio in the frontal cortex, 
      striatum, and hippocampus. In contrast, a single administration of (R)-ketamine 
      significantly increased the D-serine/L-serine ratio in the frontal cortex. 
      CONCLUSIONS: These results suggested that alterations in the tissue levels of 
      these amino acids may be involved in the antidepressant-like effects of the 
      combination of brexpiprazole and fluoxetine.
FAU - Ma, Min
AU  - Ma M
AD  - Division of Clinical Neuroscience, Chiba University Center for Forensic Mental 
      Health, 1-8-1 Inohana, Chiba, 260-8670, Japan.
FAU - Ren, Qian
AU  - Ren Q
AD  - Division of Clinical Neuroscience, Chiba University Center for Forensic Mental 
      Health, 1-8-1 Inohana, Chiba, 260-8670, Japan.
FAU - Fujita, Yuko
AU  - Fujita Y
AD  - Division of Clinical Neuroscience, Chiba University Center for Forensic Mental 
      Health, 1-8-1 Inohana, Chiba, 260-8670, Japan.
FAU - Yang, Chun
AU  - Yang C
AD  - Division of Clinical Neuroscience, Chiba University Center for Forensic Mental 
      Health, 1-8-1 Inohana, Chiba, 260-8670, Japan.
FAU - Dong, Chao
AU  - Dong C
AD  - Division of Clinical Neuroscience, Chiba University Center for Forensic Mental 
      Health, 1-8-1 Inohana, Chiba, 260-8670, Japan.
FAU - Ohgi, Yuta
AU  - Ohgi Y
AD  - Department of CNS Research, New Drug Research Division, Otsuka Pharmaceutical 
      Co., Ltd., Tokushima, Japan.
FAU - Futamura, Takashi
AU  - Futamura T
AD  - Department of CNS Research, New Drug Research Division, Otsuka Pharmaceutical 
      Co., Ltd., Tokushima, Japan.
FAU - Hashimoto, Kenji
AU  - Hashimoto K
AD  - Division of Clinical Neuroscience, Chiba University Center for Forensic Mental 
      Health, 1-8-1 Inohana, Chiba, 260-8670, Japan. hashimoto@faculty.chiba-u.jp.
LA  - eng
PT  - Journal Article
DEP - 20170726
PL  - Germany
TA  - Psychopharmacology (Berl)
JT  - Psychopharmacology
JID - 7608025
RN  - 0 (Amino Acids)
RN  - 0 (Antidepressive Agents)
RN  - 0 (Quinolones)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 0 (Thiophenes)
RN  - 01K63SUP8D (Fluoxetine)
RN  - 2J3YBM1K8C (brexpiprazole)
RN  - 690G0D6V8H (Ketamine)
SB  - IM
MH  - Administration, Oral
MH  - Amino Acids/*metabolism
MH  - Animals
MH  - Antidepressive Agents/*pharmacology
MH  - Brain/*drug effects
MH  - Depressive Disorder, Major/drug therapy
MH  - Fluoxetine/*pharmacology
MH  - Ketamine/*pharmacology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Quinolones/*pharmacology
MH  - Receptors, N-Methyl-D-Aspartate/drug effects
MH  - Thiophenes/*pharmacology
OTO - NOTNLM
OT  - (R)-Ketamine
OT  - Brexpiprazole
OT  - D-Serine
OT  - GABA
OT  - Glutamate
EDAT- 2017/07/28 06:00
MHDA- 2018/05/15 06:00
CRDT- 2017/07/28 06:00
PHST- 2017/04/11 00:00 [received]
PHST- 2017/07/17 00:00 [accepted]
PHST- 2017/07/28 06:00 [pubmed]
PHST- 2018/05/15 06:00 [medline]
PHST- 2017/07/28 06:00 [entrez]
AID - 10.1007/s00213-017-4700-z [pii]
AID - 10.1007/s00213-017-4700-z [doi]
PST - ppublish
SO  - Psychopharmacology (Berl). 2017 Nov;234(21):3165-3173. doi: 
      10.1007/s00213-017-4700-z. Epub 2017 Jul 26.