BDNF-mediated regulation of ethanol consumption requires the activation of the MAP kinase pathway and protein synthesis

Authors

  • Jerome Jeanblanc,

    1. The Gallo Research Center, University of California, San Francisco, Emeryville, CA, USA
    Current affiliation:
    1. Research Group on Alcohol and Pharmacodependence (GRAP) – INSERM ERI 24 – SFR Cap Sante - Pharmacy School, Universite de Picardie Jules Verne, Amiens, France
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  • Marian L. Logrip,

    1. The Gallo Research Center, University of California, San Francisco, Emeryville, CA, USA
    Current affiliation:
    1. Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, CA, USA
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  • Patricia H. Janak,

    1. The Gallo Research Center, University of California, San Francisco, Emeryville, CA, USA
    2. Department of Neurology, University of California, San Francisco, Emeryville, CA, USA
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  • Dorit Ron

    Corresponding author
    1. Department of Neurology, University of California, San Francisco, Emeryville, CA, USA
    • The Gallo Research Center, University of California, San Francisco, Emeryville, CA, USA
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Correspondence: Dorit Ron, Ph.D., 1The Gallo Research Center, as above. E-mail: dron@gallo.ucsf.edu

Abstract

We previously found that the brain-derived neurotrophic factor (BDNF) in the dorsolateral striatum (DLS) is part of a homeostatic pathway that gates ethanol self-administration [Jeanblanc et al. (2009). J Neurosci, 29, 13494–13502)]. Specifically, we showed that moderate levels (10%) of ethanol consumption increase BDNF expression within the DLS, and that direct infusion of BDNF into the DLS decreases operant self-administration of a 10% ethanol solution. BDNF binding to its receptor, TrkB, activates the mitogen-activated protein kinase (MAPK), phospholipase C-γ (PLC-γ) and phosphatidylinositol 3-kinase (PI3K) pathways. Thus, here, we set out to identify which of these intracellular pathway(s) plays a role in the regulation of ethanol consumption by BDNF. We found that inhibition of the MAPK, but not PLC-γ or PI3K, activity blocks the BDNF-mediated reduction of ethanol consumption. As activation of the MAPK pathway leads to the initiation of transcription and/or translation events, we tested whether the BDNF-mediated reduction of ethanol self-administration requires de novo protein synthesis. We found that the inhibitory effect of BDNF on ethanol intake is blocked by the protein synthesis inhibitor cycloheximide. Together, our results show that BDNF attenuates ethanol drinking via activation of the MAPK pathway in a protein synthesis-dependent manner within the DLS.

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