PMID- 24899712
OWN - NLM
STAT- MEDLINE
DCOM- 20140725
LR  - 20240327
IS  - 1529-2401 (Electronic)
IS  - 0270-6474 (Print)
IS  - 0270-6474 (Linking)
VI  - 34
IP  - 23
DP  - 2014 Jun 4
TI  - BDNF signaling in the VTA links the drug-dependent state to drug withdrawal 
      aversions.
PG  - 7899-909
LID - 10.1523/JNEUROSCI.3776-13.2014 [doi]
AB  - Drug administration to avoid unpleasant drug withdrawal symptoms has been 
      hypothesized to be a crucial factor that leads to compulsive drug-taking 
      behavior. However, the neural relationship between the aversive motivational 
      state produced by drug withdrawal and the development of the drug-dependent state 
      still remains elusive. It has been observed that chronic exposure to drugs of 
      abuse increases brain-derived neurotrophic factor (BDNF) levels in ventral 
      tegmental area (VTA) neurons. In particular, BDNF expression is dramatically 
      increased during drug withdrawal, which would suggest a direct connection between 
      the aversive state of withdrawal and BDNF-induced neuronal plasticity. Using 
      lentivirus-mediated gene transfer to locally knock down the expression of the 
      BDNF receptor tropomyosin-receptor-kinase type B in rats and mice, we observed 
      that chronic opiate administration activates BDNF-related neuronal plasticity in 
      the VTA that is necessary for both the establishment of an opiate-dependent state 
      and aversive withdrawal motivation. Our findings highlight the importance of a 
      bivalent, plastic mechanism that drives the negative reinforcement underlying 
      addiction.
CI  - Copyright (c) 2014 the authors 0270-6474/14/347899-11$15.00/0.
FAU - Vargas-Perez, Hector
AU  - Vargas-Perez H
AD  - Department of Molecular Genetics, Neurobiology Research Group, University of 
      Toronto, Toronto, Ontario, M5S3E1 Canada, vargashector@yahoo.com.
FAU - Bahi, Amine
AU  - Bahi A
AD  - Department of Anatomy, Faculty of Medicine and Health Sciences, United Arab 
      Emirates University, Alabama Ain, 17666 United Arab Emirates.
FAU - Bufalino, Mary Rose
AU  - Bufalino MR
AD  - Department of Medical Biophysics, Terrence Donnelly Centre for Cellular and 
      Biomolecular Research, University of Toronto, Toronto, Ontario, M5S3E1 Canada.
FAU - Ting-A-Kee, Ryan
AU  - Ting-A-Kee R
AD  - Department of Molecular Genetics, Neurobiology Research Group, University of 
      Toronto, Toronto, Ontario, M5S3E1 Canada.
FAU - Maal-Bared, Geith
AU  - Maal-Bared G
AD  - Department of Molecular Genetics, Neurobiology Research Group, University of 
      Toronto, Toronto, Ontario, M5S3E1 Canada.
FAU - Lam, Jenny
AU  - Lam J
AD  - Department of Molecular Genetics, Neurobiology Research Group, University of 
      Toronto, Toronto, Ontario, M5S3E1 Canada.
FAU - Fahmy, Ahmed
AU  - Fahmy A
AD  - Department of Molecular Genetics, Neurobiology Research Group, University of 
      Toronto, Toronto, Ontario, M5S3E1 Canada.
FAU - Clarke, Laura
AU  - Clarke L
AD  - Department of Molecular Genetics, Neurobiology Research Group, University of 
      Toronto, Toronto, Ontario, M5S3E1 Canada.
FAU - Blanchard, Jennifer K
AU  - Blanchard JK
AD  - Department of Psychology and Center for Neuroscience, Brigham Young University, 
      Provo, UT 84602, and.
FAU - Larsen, Brett R
AU  - Larsen BR
AD  - Department of Psychology and Center for Neuroscience, Brigham Young University, 
      Provo, UT 84602, and.
FAU - Steffensen, Scott
AU  - Steffensen S
AD  - Department of Psychology and Center for Neuroscience, Brigham Young University, 
      Provo, UT 84602, and.
FAU - Dreyer, Jean-Luc
AU  - Dreyer JL
AD  - Department of Medicine, Division of Biochemistry, University of Fribourg, 
      Fribourg 1700, Switzerland.
FAU - van der Kooy, Derek
AU  - van der Kooy D
AD  - Department of Molecular Genetics, Neurobiology Research Group, University of 
      Toronto, Toronto, Ontario, M5S3E1 Canada, Department of Medical Biophysics, 
      Terrence Donnelly Centre for Cellular and Biomolecular Research, University of 
      Toronto, Toronto, Ontario, M5S3E1 Canada.
LA  - eng
GR  - R01 AA020919/AA/NIAAA NIH HHS/United States
GR  - R01 DA035958/DA/NIDA NIH HHS/United States
GR  - AA020919/AA/NIAAA NIH HHS/United States
GR  - 53893/CAPMC/CIHR/Canada
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Neurosci
JT  - The Journal of neuroscience : the official journal of the Society for 
      Neuroscience
JID - 8102140
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Narcotics)
RN  - 70D95007SX (Heroin)
RN  - EC 4.1.1.15 (Glutamate Decarboxylase)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/*metabolism/pharmacology
MH  - Disease Models, Animal
MH  - Gene Expression Regulation/drug effects/genetics
MH  - Glutamate Decarboxylase/genetics
MH  - Heroin/administration & dosage/adverse effects
MH  - In Vitro Techniques
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Narcotics/administration & dosage/adverse effects
MH  - Opioid-Related Disorders/metabolism/*pathology
MH  - Rats
MH  - Rats, Wistar
MH  - Signal Transduction/drug effects/genetics/*physiology
MH  - Substance Withdrawal Syndrome/metabolism/*pathology
MH  - Ventral Tegmental Area/drug effects/*metabolism
PMC - PMC4099491
OTO - NOTNLM
OT  - BDNF
OT  - TrkB
OT  - dependent state
OT  - drug addiction
OT  - opiates
OT  - withdrawal
EDAT- 2014/06/06 06:00
MHDA- 2014/07/26 06:00
PMCR- 2014/12/04
CRDT- 2014/06/06 06:00
PHST- 2014/06/06 06:00 [entrez]
PHST- 2014/06/06 06:00 [pubmed]
PHST- 2014/07/26 06:00 [medline]
PHST- 2014/12/04 00:00 [pmc-release]
AID - 34/23/7899 [pii]
AID - 3776-13 [pii]
AID - 10.1523/JNEUROSCI.3776-13.2014 [doi]
PST - ppublish
SO  - J Neurosci. 2014 Jun 4;34(23):7899-909. doi: 10.1523/JNEUROSCI.3776-13.2014.