PMID- 24582917
OWN - NLM
STAT- MEDLINE
DCOM- 20140609
LR  - 20151119
IS  - 1090-2430 (Electronic)
IS  - 0014-4886 (Linking)
VI  - 255
DP  - 2014 May
TI  - Brain-derived neurotrophic factor in the amygdala mediates susceptibility to fear 
      conditioning.
PG  - 19-29
LID - S0014-4886(14)00061-2 [pii]
LID - 10.1016/j.expneurol.2014.02.016 [doi]
AB  - Fear conditioning in animals has been used extensively to model clinical anxiety 
      disorders. While individual animals exhibit marked differences in their 
      propensity to undergo fear conditioning, the physiologically relevant mediators 
      have not yet been fully characterized. Here, we demonstrate that C57BL/6 inbred 
      mouse strain subjected to a regimen of chronic social defeat stress (CSDS) can be 
      separated into susceptible and resistant subpopulations that display different 
      levels of fear responses in an auditory fear conditioning paradigm. Susceptible 
      mice had significantly more c-Fos protein expression in neurons of the 
      basolateral amygdala (BLA) following CSDS and showed exaggerated conditioned fear 
      responses, while there were no significant differences between groups in innate 
      anxiety- and depressive-like behaviors. Through the use of conditional 
      brain-derived neurotrophic factor (BDNF) knockout strategies, we find that 
      elevated BLA BDNF level following fear conditioning training is a key mediator 
      contributing to determine the levels of conditioned fear responses. Our results 
      also show that relative to susceptible mice, resistant mice had a much faster 
      recovery from conditioned stimuli-induced cardiovascular and corticosterone 
      responses. Systemic administration of norepinephrine reuptake inhibitor 
      atomoxetine increased c-Fos protein expression in BLA neurons following fear 
      conditioning training and promoted the expression of conditioned fear in 
      resistant mice. Conversely, administration of beta-adrenergic receptor antagonist 
      propranolol reduced fear conditioning training-induced c-Fos protein expression 
      in BLA neurons and reduced conditioned fear responses in susceptible mice. These 
      findings reveal a novel role for the BDNF signaling within the BLA in mediating 
      individual differences in autonomic, neuroendocrine and behavioral reactivity to 
      fear conditioning.
CI  - Copyright (c) 2014 Elsevier Inc. All rights reserved.
FAU - Chou, Dylan
AU  - Chou D
AD  - Department of Pharmacology, College of Medicine, National Cheng Kung University, 
      Tainan 701, Taiwan; Institute of Basic Medical Sciences, College of Medicine, 
      National Cheng Kung University, Tainan 701, Taiwan.
FAU - Huang, Chiung-Chun
AU  - Huang CC
AD  - Department of Pharmacology, College of Medicine, National Cheng Kung University, 
      Tainan 701, Taiwan.
FAU - Hsu, Kuei-Sen
AU  - Hsu KS
AD  - Department of Pharmacology, College of Medicine, National Cheng Kung University, 
      Tainan 701, Taiwan; Institute of Basic Medical Sciences, College of Medicine, 
      National Cheng Kung University, Tainan 701, Taiwan. Electronic address: 
      richard@mail.ncku.edu.tw.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140225
PL  - United States
TA  - Exp Neurol
JT  - Experimental neurology
JID - 0370712
RN  - 0 (Adrenergic Uptake Inhibitors)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Propylamines)
RN  - 0 (Proto-Oncogene Proteins c-fos)
RN  - 57WVB6I2W0 (Atomoxetine Hydrochloride)
SB  - IM
MH  - Acoustic Stimulation
MH  - Adrenergic Uptake Inhibitors/pharmacology
MH  - Amygdala/drug effects/*metabolism
MH  - Animals
MH  - Association Learning/drug effects/*physiology
MH  - Atomoxetine Hydrochloride
MH  - Brain-Derived Neurotrophic Factor/genetics/*metabolism
MH  - Conditioning, Classical/drug effects/*physiology
MH  - Fear/drug effects/*physiology
MH  - Male
MH  - Mice
MH  - Mice, Knockout
MH  - Neurons/drug effects/metabolism
MH  - Propylamines/pharmacology
MH  - Proto-Oncogene Proteins c-fos/metabolism
OTO - NOTNLM
OT  - Amygdala
OT  - Anxiety
OT  - BDNF
OT  - Fear conditioning
OT  - Social defeat stress
EDAT- 2014/03/04 06:00
MHDA- 2014/06/10 06:00
CRDT- 2014/03/04 06:00
PHST- 2013/10/08 00:00 [received]
PHST- 2014/02/07 00:00 [revised]
PHST- 2014/02/11 00:00 [accepted]
PHST- 2014/03/04 06:00 [entrez]
PHST- 2014/03/04 06:00 [pubmed]
PHST- 2014/06/10 06:00 [medline]
AID - S0014-4886(14)00061-2 [pii]
AID - 10.1016/j.expneurol.2014.02.016 [doi]
PST - ppublish
SO  - Exp Neurol. 2014 May;255:19-29. doi: 10.1016/j.expneurol.2014.02.016. Epub 2014 
      Feb 25.