PMID- 17618281
OWN - NLM
STAT- MEDLINE
DCOM- 20071107
LR  - 20220309
IS  - 1097-6256 (Print)
IS  - 1097-6256 (Linking)
VI  - 10
IP  - 8
DP  - 2007 Aug
TI  - Dynamic BDNF activity in nucleus accumbens with cocaine use increases 
      self-administration and relapse.
PG  - 1029-37
AB  - A single exposure to cocaine rapidly induces the brief activation of several 
      immediate early genes, but the role of such short-term regulation in the enduring 
      consequences of cocaine use is poorly understood. We found that 4 h of 
      intravenous cocaine self-administration in rats induced a transient increase in 
      brain-derived neurotrophic factor (BDNF) and activation of TrkB-mediated 
      signaling in the nucleus accumbens (NAc). Augmenting this dynamic regulation with 
      five daily NAc BDNF infusions caused enduring increases in cocaine 
      self-administration, and facilitated relapse to cocaine seeking in withdrawal. In 
      contrast, neutralizing endogenous BDNF regulation with intra-NAc infusions of 
      antibody to BDNF subsequently reduced cocaine self-administration and attenuated 
      relapse. Using localized inducible BDNF knockout in mice, we found that BDNF 
      originating from NAc neurons was necessary for maintaining increased cocaine 
      self-administration. These findings suggest that dynamic induction and release of 
      BDNF from NAc neurons during cocaine use promotes the development and persistence 
      of addictive behavior.
FAU - Graham, Danielle L
AU  - Graham DL
AD  - Department of Psychiatry, The Seay Center for Basic and Applied Research in 
      Psychiatric Illness, The University of Texas Southwestern Medical Center, Dallas, 
      Texas 75390-9070, USA.
FAU - Edwards, Scott
AU  - Edwards S
FAU - Bachtell, Ryan K
AU  - Bachtell RK
FAU - DiLeone, Ralph J
AU  - DiLeone RJ
FAU - Rios, Maribel
AU  - Rios M
FAU - Self, David W
AU  - Self DW
LA  - eng
GR  - DA 016857/DA/NIDA NIH HHS/United States
GR  - DA 08227/DA/NIDA NIH HHS/United States
GR  - DA 10460/DA/NIDA NIH HHS/United States
GR  - DA 18743/DA/NIDA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20070708
PL  - United States
TA  - Nat Neurosci
JT  - Nature neuroscience
JID - 9809671
RN  - 0 (Anesthetics, Local)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - I5Y540LHVR (Cocaine)
SB  - IM
CIN - Nat Neurosci. 2007 Aug;10(8):935-6. PMID: 17657232
MH  - Analysis of Variance
MH  - Anesthetics, Local/*administration & dosage
MH  - Animals
MH  - Behavior, Animal/drug effects
MH  - Brain-Derived Neurotrophic Factor/deficiency/genetics/*metabolism
MH  - Cocaine/*administration & dosage
MH  - Cocaine-Related Disorders/metabolism/physiopathology
MH  - Conditioning, Operant/drug effects
MH  - Dose-Response Relationship, Drug
MH  - Gene Expression Regulation/*drug effects
MH  - Male
MH  - Mice
MH  - Mice, Knockout
MH  - Motor Activity/drug effects
MH  - Neurons/drug effects/metabolism
MH  - Nucleus Accumbens/cytology/*drug effects
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptor, trkB/metabolism
MH  - *Reinforcement, Psychology
MH  - Self Administration/methods
MH  - Time Factors
EDAT- 2007/07/10 09:00
MHDA- 2007/11/08 09:00
CRDT- 2007/07/10 09:00
PHST- 2007/01/19 00:00 [received]
PHST- 2007/05/30 00:00 [accepted]
PHST- 2007/07/10 09:00 [pubmed]
PHST- 2007/11/08 09:00 [medline]
PHST- 2007/07/10 09:00 [entrez]
AID - nn1929 [pii]
AID - 10.1038/nn1929 [doi]
PST - ppublish
SO  - Nat Neurosci. 2007 Aug;10(8):1029-37. doi: 10.1038/nn1929. Epub 2007 Jul 8.