Journal article

BDNF signaling in the VTA links the drug-dependent state to drug withdrawal aversions

  • Vargas-Perez, Hector Department of Molecular Genetics, Neurobiology Research Group, University of Toronto, Canada,
  • Bahi, Amine Department of Anatomy, Faculty of Medicine and Health Sciences, United Arab Emirates University, Alabama Ain, United Arab Emirates,
  • Bufalino, Mary Rose Department of Medical Biophysics, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Canada,
  • Ting-A-Kee, Ryan Department of Molecular Genetics, Neurobiology Research Group, University of Toronto, Canada,
  • Maal-Bared, Geith Department of Molecular Genetics, Neurobiology Research Group, University of Toronto, Canada,
  • Lam, Jenny Department of Molecular Genetics, Neurobiology Research Group, University of Toronto, Canada,
  • Fahmy, Ahmed Department of Molecular Genetics, Neurobiology Research Group, University of Toronto, Canada,
  • Clarke, Laura Department of Molecular Genetics, Neurobiology Research Group, University of Toronto, Canada,
  • Blanchard, Jennifer K. Department of Psychology and Center for Neuroscience, Brigham Young University, Provo, Canada
  • Larsen, Brett R. Department of Psychology and Center for Neuroscience, Brigham Young University, Provo, Canada
  • Steffensen, Scott Department of Psychology and Center for Neuroscience, Brigham Young University, Provo, Canada
  • Dreyer, Jean-Luc Department of Medicine, Division of Biochemistry, University of Fribourg, Switzerland
  • Kooy, Derek van der Department of Molecular Genetics, Neurobiology Research Group, University of Toronto, Canada,
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    06.04.2014
Published in:
  • The Journal of Neuroscience. - 2014, vol. 34, no. 23, p. 7899–7909
English 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.
Faculty
Faculté des sciences et de médecine
Department
Département de Médecine
Language
  • English
Classification
Biology
License
License undefined
Identifiers
Persistent URL
https://folia.unifr.ch/unifr/documents/303557
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