PMID- 28808012
OWN - NLM
STAT- MEDLINE
DCOM- 20180530
LR  - 20200930
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 114
IP  - 35
DP  - 2017 Aug 29
TI  - BDNF-TrkB controls cocaine-induced dendritic spines in rodent nucleus accumbens 
      dissociated from increases in addictive behaviors.
PG  - 9469-9474
LID - 10.1073/pnas.1702441114 [doi]
AB  - Chronic cocaine use is associated with prominent morphological changes in nucleus 
      accumbens shell (NACsh) neurons, including increases in dendritic spine density 
      along with enhanced motivation for cocaine, but a functional relationship between 
      these morphological and behavioral phenomena has not been shown. Here we show 
      that brain-derived neurotrophic factor (BDNF) signaling through tyrosine kinase B 
      (TrkB) receptors in NACsh neurons is necessary for cocaine-induced dendritic 
      spine formation by using either localized TrkB knockout or viral-mediated 
      expression of a dominant negative, kinase-dead TrkB mutant. Interestingly, 
      augmenting wild-type TrkB expression after chronic cocaine self-administration 
      reverses the sustained increase in dendritic spine density, an effect mediated by 
      TrkB signaling pathways that converge on extracellular regulated kinase. Loss of 
      TrkB function after cocaine self-administration, however, leaves spine density 
      intact but markedly enhances the motivation for cocaine, an effect mediated by 
      specific loss of TrkB signaling through phospholipase Cgamma1 (PLCgamma1). 
      Conversely, overexpression of PLCgamma1 both reduces the motivation for cocaine and 
      reverses dendritic spine density, suggesting a potential target for the treatment 
      of addiction in chronic users. Together, these findings indicate that BDNF-TrkB 
      signaling both mediates and reverses cocaine-induced increases in dendritic spine 
      density in NACsh neurons, and these morphological changes are entirely 
      dissociable from changes in addictive behavior.
FAU - Anderson, Ethan M
AU  - Anderson EM
AD  - Department of Psychiatry, The Seay Center for Basic and Applied Research in 
      Psychiatric Illness, UT Southwestern Medical Center, Dallas, TX 75390.
FAU - Wissman, Anne Marie
AU  - Wissman AM
AD  - Department of Psychiatry, The Seay Center for Basic and Applied Research in 
      Psychiatric Illness, UT Southwestern Medical Center, Dallas, TX 75390.
FAU - Chemplanikal, Joyce
AU  - Chemplanikal J
AD  - Department of Psychiatry, The Seay Center for Basic and Applied Research in 
      Psychiatric Illness, UT Southwestern Medical Center, Dallas, TX 75390.
FAU - Buzin, Nicole
AU  - Buzin N
AD  - Department of Psychiatry, The Seay Center for Basic and Applied Research in 
      Psychiatric Illness, UT Southwestern Medical Center, Dallas, TX 75390.
FAU - Guzman, Daniel
AU  - Guzman D
AD  - Department of Psychiatry, The Seay Center for Basic and Applied Research in 
      Psychiatric Illness, UT Southwestern Medical Center, Dallas, TX 75390.
FAU - Larson, Erin B
AU  - Larson EB
AD  - Department of Psychiatry, The Seay Center for Basic and Applied Research in 
      Psychiatric Illness, UT Southwestern Medical Center, Dallas, TX 75390.
FAU - Neve, Rachael L
AU  - Neve RL
AD  - Viral Gene Transfer Core, Massachusetts Institute of Technology, Cambridge, MA 
      02139.
FAU - Nestler, Eric J
AU  - Nestler EJ
AD  - Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY 
      10029.
FAU - Cowan, Christopher W
AU  - Cowan CW
AD  - Department of Neuroscience, Medical University of South Carolina, Charleston, SC 
      29425.
FAU - Self, David W
AU  - Self DW
AD  - Department of Psychiatry, The Seay Center for Basic and Applied Research in 
      Psychiatric Illness, UT Southwestern Medical Center, Dallas, TX 75390; 
      david.self@utsouthwestern.edu.
LA  - eng
GR  - T32 DA007290/DA/NIDA NIH HHS/United States
GR  - R01 DA032708/DA/NIDA NIH HHS/United States
GR  - P01 DA008227/DA/NIDA NIH HHS/United States
GR  - R01 DA014133/DA/NIDA NIH HHS/United States
GR  - R01 DA040620/DA/NIDA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20170814
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - EC 2.7.10.1 (Ntrk2 protein, rat)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - I5Y540LHVR (Cocaine)
RN  - U8CJK0JH5M (Anthralin)
SB  - IM
MH  - Animals
MH  - Anthralin
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Cocaine/*pharmacology
MH  - *Cocaine-Related Disorders
MH  - Dendritic Spines/*drug effects
MH  - HEK293 Cells
MH  - Humans
MH  - Male
MH  - Neurons/physiology
MH  - Nucleus Accumbens/cytology/*physiology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptor, trkB/genetics/*metabolism
MH  - Signal Transduction
PMC - PMC5584417
OTO - NOTNLM
OT  - BDNF-TrkB
OT  - PLC
OT  - accumbens shell
OT  - cocaine addiction
OT  - dendritic spines
COIS- The authors declare no conflict of interest.
EDAT- 2017/08/16 06:00
MHDA- 2018/05/31 06:00
PMCR- 2018/02/28
CRDT- 2017/08/16 06:00
PHST- 2017/08/16 06:00 [pubmed]
PHST- 2018/05/31 06:00 [medline]
PHST- 2017/08/16 06:00 [entrez]
PHST- 2018/02/28 00:00 [pmc-release]
AID - 1702441114 [pii]
AID - 201702441 [pii]
AID - 10.1073/pnas.1702441114 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2017 Aug 29;114(35):9469-9474. doi: 
      10.1073/pnas.1702441114. Epub 2017 Aug 14.