Infusion of brain-derived neurotrophic factor into the ventral tegmental area switches the substrates mediating ethanol motivation

Authors

  • Ryan Ting-A-Kee,

    Corresponding author
    • Institute of Medical Science, University of Toronto, Toronto, ON, Canada
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  • Hector Vargas-Perez,

    1. Department of Molecular Genetics, Neurobiology Research Group, University of Toronto, Toronto, ON, Canada
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  • Mary-Rose Bufalino,

    1. Department of Medical Biophysics, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada
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  • Amine Bahi,

    1. Department of Anatomy, Faculty of Medicine and Health Sciences, United Arab Emirates University, Al Ain, UAE
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  • Jean-Luc Dreyer,

    1. Department of Medicine, Division of Biochemistry, University of Fribourg, Fribourg, Switzerland
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  • Rachel F. Tyndale,

    1. Centre for Addiction and Mental Health, Departments of Psychiatry, Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada
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  • Derek van der Kooy

    1. Institute of Medical Science, University of Toronto, Toronto, ON, Canada
    2. Department of Molecular Genetics, Neurobiology Research Group, University of Toronto, Toronto, ON, Canada
    3. Department of Medical Biophysics, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada
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Correspondence: Ryan Ting-A-Kee, as above.

E-mail: ryan.ting.a.kee@utoronto.ca

Abstract

Recent work has shown that infusion of brain-derived neurotrophic factor (BDNF) into the ventral tegmental area (VTA) promotes a switch in the mechanisms mediating morphine motivation, from a dopamine-independent to a dopamine-dependent pathway. Here we showed that a single infusion of intra-VTA BDNF also promoted a switch in the mechanisms mediating ethanol motivation, from a dopamine-dependent to a dopamine-independent pathway (exactly opposite to that seen with morphine). We suggest that intra-VTA BDNF, via its actions on TrkB receptors, precipitates a switch similar to that which occurs naturally when mice transit from a drug-naive, non-deprived state to a drug-deprived state. The opposite switching of the mechanisms underlying morphine and ethanol motivation by BDNF in previously non-deprived animals is consistent with their proposed actions on VTA GABAA receptors.

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