PMID- 30243915
OWN - NLM
STAT- MEDLINE
DCOM- 20190225
LR  - 20211204
IS  - 1873-7064 (Electronic)
IS  - 0028-3908 (Linking)
VI  - 143
DP  - 2018 Dec
TI  - Mechanism underlying NMDA blockade-induced inhibition of aggression in 
      post-weaning socially isolated mice.
PG  - 95-105
LID - S0028-3908(18)30658-0 [pii]
LID - 10.1016/j.neuropharm.2018.09.019 [doi]
AB  - When faced with stressful conditions, people with a tendency toward impulsive 
      aggression may suddenly hurt others. We have previously shown that the blockade 
      of NMDA receptors (NMDARs) within the ventral hippocampus (VH) produces 
      anti-aggressive effects. However, little is known about the mechanism for tamping 
      down stress-provoked attack behavior. Here, we report that expression of 
      brain-derived neurotrophic factor (BDNF) after inhibition of NMDARs in the VH is 
      required for blunting stress-provoked attack behavior in post-weaning socially 
      isolated mice. Administration of NMDAR antagonist MK-801 decreased the 
      phosphorylated eukaryotic elongation factor 2 (p-eEF2) and increased BDNF 
      expression in the VH. Infusion of eEF2 kinase inhibitor NH125 to the VH decreased 
      attack behavior and increased BDNF expression. Knockdown of BDNF in the VH 
      blocked the anti-aggressive effect of MK-801 and NH125. Furthermore, MK-801 
      rapidly increased the activity of protein phosphatase 2A (PP2A). Intra-VH 
      infusion of PP2A inhibitor okadaic acid blocked the anti-aggressive effects of 
      MK-801. These results suggest that blockade of NMDAR reduces attack behavior 
      through increasing PP2A activity leading to dephosphorylation of eEF2 and an 
      increase in BDNF expression. Our findings indicate that the enhancement of BDNF 
      expression is beneficial for preventing impulsive aggression in at-risk beings.
CI  - Copyright (c) 2018 Elsevier Ltd. All rights reserved.
FAU - Chang, Chih-Hua
AU  - Chang CH
AD  - Department of Pharmacology, National Cheng-Kung University, Tainan, 701, Taiwan.
FAU - Su, Chun-Lin
AU  - Su CL
AD  - Department of Pharmacology, National Cheng-Kung University, Tainan, 701, Taiwan.
FAU - Gean, Po-Wu
AU  - Gean PW
AD  - Department of Pharmacology, National Cheng-Kung University, Tainan, 701, Taiwan. 
      Electronic address: powu@mail.ncku.edu.tw.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180920
PL  - England
TA  - Neuropharmacology
JT  - Neuropharmacology
JID - 0236217
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Excitatory Amino Acid Antagonists)
RN  - 0 (Psychotropic Drugs)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 6LR8C1B66Q (Dizocilpine Maleate)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.20 (Eef2k protein, mouse)
RN  - EC 2.7.11.20 (Elongation Factor 2 Kinase)
RN  - EC 3.1.3.16 (Protein Phosphatase 2)
SB  - IM
MH  - Aggression/*drug effects/physiology
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - Dizocilpine Maleate/*pharmacology
MH  - Elongation Factor 2 Kinase/metabolism
MH  - Excitatory Amino Acid Antagonists/*pharmacology
MH  - Gene Expression Regulation/drug effects
MH  - Hippocampus/drug effects/metabolism
MH  - Impulsive Behavior/drug effects/physiology
MH  - Male
MH  - Mice, Inbred C57BL
MH  - Protein Phosphatase 2/antagonists & inhibitors/metabolism
MH  - Psychotropic Drugs/*pharmacology
MH  - Receptors, N-Methyl-D-Aspartate/*antagonists & inhibitors/metabolism
MH  - *Social Isolation/psychology
MH  - Stress, Psychological/drug therapy/metabolism
MH  - TOR Serine-Threonine Kinases/metabolism
OTO - NOTNLM
OT  - Aggression
OT  - BDNF
OT  - NMDA receptor
OT  - PP2A
OT  - Ventral hippocampus
OT  - eEF2
EDAT- 2018/09/24 06:00
MHDA- 2019/02/26 06:00
CRDT- 2018/09/24 06:00
PHST- 2018/03/21 00:00 [received]
PHST- 2018/08/22 00:00 [revised]
PHST- 2018/09/11 00:00 [accepted]
PHST- 2018/09/24 06:00 [pubmed]
PHST- 2019/02/26 06:00 [medline]
PHST- 2018/09/24 06:00 [entrez]
AID - S0028-3908(18)30658-0 [pii]
AID - 10.1016/j.neuropharm.2018.09.019 [doi]
PST - ppublish
SO  - Neuropharmacology. 2018 Dec;143:95-105. doi: 10.1016/j.neuropharm.2018.09.019. 
      Epub 2018 Sep 20.