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FMRP regulates an ethanol-dependent shift in GABABR function and expression with rapid antidepressant properties

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  • Sarah A. Wolfe

    (Waggoner Center for Alcohol and Addiction Research, The University of Texas at Austin
    Center for Learning and Memory, The University of Texas at Austin
    Institute of Cell and Molecular Biology, The University of Texas at Austin)

  • Emily R. Workman

    (Center for Learning and Memory, The University of Texas at Austin
    The University of Texas at Austin)

  • Chelcie F. Heaney

    (Center for Learning and Memory, The University of Texas at Austin
    The University of Texas at Austin)

  • Farr Niere

    (Center for Learning and Memory, The University of Texas at Austin
    The University of Texas at Austin)

  • Sanjeev Namjoshi

    (Center for Learning and Memory, The University of Texas at Austin
    Institute of Cell and Molecular Biology, The University of Texas at Austin)

  • Luisa P. Cacheaux

    (Center for Learning and Memory, The University of Texas at Austin
    The University of Texas at Austin)

  • Sean P. Farris

    (Waggoner Center for Alcohol and Addiction Research, The University of Texas at Austin
    The University of Texas at Austin)

  • Michael R. Drew

    (Center for Learning and Memory, The University of Texas at Austin
    Institute of Cell and Molecular Biology, The University of Texas at Austin
    The University of Texas at Austin)

  • Boris V. Zemelman

    (Center for Learning and Memory, The University of Texas at Austin
    Institute of Cell and Molecular Biology, The University of Texas at Austin
    The University of Texas at Austin)

  • R. Adron Harris

    (Waggoner Center for Alcohol and Addiction Research, The University of Texas at Austin
    Institute of Cell and Molecular Biology, The University of Texas at Austin
    The University of Texas at Austin)

  • Kimberly F. Raab-Graham

    (Waggoner Center for Alcohol and Addiction Research, The University of Texas at Austin
    Center for Learning and Memory, The University of Texas at Austin
    Institute of Cell and Molecular Biology, The University of Texas at Austin
    The University of Texas at Austin)

Abstract

Alcohol promotes lasting neuroadaptive changes that may provide relief from depressive symptoms, often referred to as the self-medication hypothesis. However, the molecular/synaptic pathways that are shared by alcohol and antidepressants are unknown. In the current study, acute exposure to ethanol produced lasting antidepressant and anxiolytic behaviours. To understand the functional basis of these behaviours, we examined a molecular pathway that is activated by rapid antidepressants. Ethanol, like rapid antidepressants, alters γ-aminobutyric acid type B receptor (GABABR) expression and signalling, to increase dendritic calcium. Furthermore, new GABABRs are synthesized in response to ethanol treatment, requiring fragile-X mental retardation protein (FMRP). Ethanol-dependent changes in GABABR expression, dendritic signalling, and antidepressant efficacy are absent in Fmr1-knockout (KO) mice. These findings indicate that FMRP is an important regulator of protein synthesis following alcohol exposure, providing a molecular basis for the antidepressant efficacy of acute ethanol exposure.

Suggested Citation

  • Sarah A. Wolfe & Emily R. Workman & Chelcie F. Heaney & Farr Niere & Sanjeev Namjoshi & Luisa P. Cacheaux & Sean P. Farris & Michael R. Drew & Boris V. Zemelman & R. Adron Harris & Kimberly F. Raab-Gr, 2016. "FMRP regulates an ethanol-dependent shift in GABABR function and expression with rapid antidepressant properties," Nature Communications, Nature, vol. 7(1), pages 1-13, November.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms12867
    DOI: 10.1038/ncomms12867
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