PMID- 26506052
OWN - NLM
STAT- MEDLINE
DCOM- 20160719
LR  - 20181113
IS  - 2158-3188 (Electronic)
IS  - 2158-3188 (Linking)
VI  - 5
IP  - 10
DP  - 2015 Oct 27
TI  - BDNF-TrkB signaling in the nucleus accumbens shell of mice has key role in 
      methamphetamine withdrawal symptoms.
PG  - e666
LID - 10.1038/tp.2015.157 [doi]
AB  - Depression is a core symptom of methamphetamine (METH) withdrawal during the 
      first several weeks of abstinence. However, the precise mechanisms underlying 
      METH withdrawal symptoms remain unknown. Brain-derived neurotrophic factor (BDNF) 
      and its specific receptor, tropomyosin-related kinase (TrkB), have a role the in 
      pathophysiology of depression. In this study, we examined the role of BDNF-TrkB 
      signaling in different brain regions of male mice with METH withdrawal symptoms. 
      Repeated METH (3 mg kg(-1) per day for 5 days) administration to mice caused a 
      long-lasting depression-like behavior including anhedonia. Western blot analysis 
      showed that BDNF levels in the nucleus accumbens (NAc) of METH-treated mice were 
      significantly higher than those of control mice whereas BDNF levels in other 
      regions, including the prefrontal cortex and hippocampus, were not altered. 
      METH-induced depression-like behavior, behavioral sensitization and dendritic 
      changes in the NAc shell were improved by subsequent subchronic administration of 
      TrkB antagonist ANA-12 (0.5 mg kg(-1) per day for 14 days), but not TrkB agonist 
      7,8-dihydroxyflavone (10 mg kg(-1) per day for 14 days). In vivo microdialysis 
      showed that METH (1 mg kg(-1))-induced dopamine release in NAc shell of 
      METH-treated mice was attenuated after subsequent subchronic ANA-12 
      administration. Interestingly, a single bilateral infusion of ANA-12 into the NAc 
      shell, but not NAc core, showed a rapid and long-lasting therapeutic effect. 
      However, ketamine and paroxetine had no effect. These findings suggest that 
      increased BDNF-TrkB signaling in the NAc shell has an important role in the 
      behavioral abnormalities after withdrawal from repeated METH administration, and 
      that TrkB antagonists are potential therapeutic drugs for withdrawal symptoms in 
      METH abusers.
FAU - Ren, Q
AU  - Ren Q
AUID- ORCID: 0000-0003-2982-8824
AD  - Division of Clinical Neuroscience, Chiba University Center for Forensic Mental 
      Health, Chiba, Japan.
FAU - Ma, M
AU  - Ma M
AD  - Division of Clinical Neuroscience, Chiba University Center for Forensic Mental 
      Health, Chiba, Japan.
FAU - Yang, C
AU  - Yang C
AD  - Division of Clinical Neuroscience, Chiba University Center for Forensic Mental 
      Health, Chiba, Japan.
FAU - Zhang, J-C
AU  - Zhang JC
AD  - Division of Clinical Neuroscience, Chiba University Center for Forensic Mental 
      Health, Chiba, Japan.
FAU - Yao, W
AU  - Yao W
AD  - Division of Clinical Neuroscience, Chiba University Center for Forensic Mental 
      Health, Chiba, Japan.
FAU - Hashimoto, K
AU  - Hashimoto K
AD  - Division of Clinical Neuroscience, Chiba University Center for Forensic Mental 
      Health, Chiba, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20151027
PL  - United States
TA  - Transl Psychiatry
JT  - Translational psychiatry
JID - 101562664
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 44RAL3456C (Methamphetamine)
RN  - 7171WSG8A2 (BDNF protein, human)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.11.28 (tropomyosin kinase)
SB  - IM
MH  - Amphetamine-Related Disorders/*metabolism
MH  - Animals
MH  - Behavior, Animal/drug effects
MH  - Blotting, Western
MH  - Brain-Derived Neurotrophic Factor/genetics/*metabolism
MH  - Disease Models, Animal
MH  - Male
MH  - Methamphetamine/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Nucleus Accumbens/drug effects/*metabolism
MH  - Protein Kinases/genetics/metabolism
MH  - Signal Transduction/*physiology
MH  - Substance Withdrawal Syndrome/*metabolism
PMC - PMC4930133
COIS- KH is an inventor on a field patent application (now pending) on 'The use of TrkB 
      antagonists in the treatment of substance abuse' by Chiba University. KH has 
      served as a scientific consultant to Astellas, Dainippon-Sumitomo and Taisho, and 
      he has also received research support from Abbvie, Dainippon-Sumitomo, Mochida, 
      Otsuka and Taisho. The remaining authors declare no conflicts of interest.
EDAT- 2015/10/28 06:00
MHDA- 2016/07/20 06:00
PMCR- 2015/10/01
CRDT- 2015/10/28 06:00
PHST- 2015/06/25 00:00 [received]
PHST- 2015/08/06 00:00 [revised]
PHST- 2015/09/06 00:00 [accepted]
PHST- 2015/10/28 06:00 [entrez]
PHST- 2015/10/28 06:00 [pubmed]
PHST- 2016/07/20 06:00 [medline]
PHST- 2015/10/01 00:00 [pmc-release]
AID - tp2015157 [pii]
AID - 10.1038/tp.2015.157 [doi]
PST - epublish
SO  - Transl Psychiatry. 2015 Oct 27;5(10):e666. doi: 10.1038/tp.2015.157.