NPY signaling inhibits extended amygdala CRF neurons to suppress binge alcohol drinking

Kristen E. Pleil, Jennifer A. Rinker, Emily G. Lowery-Gionta, Christopher M. Mazzone, Nora M. McCall, Alexis M. Kendra, David P. Olson, Bradford B. Lowell, Kathleen (Kathy) Grant, Todd E. Thiele, Thomas L. Kash

    Research output: Contribution to journalArticle

    84 Citations (Scopus)

    Abstract

    Binge alcohol drinking is a tremendous public health problem because it leads to the development of numerous pathologies, including alcohol abuse and anxiety. It is thought to do so by hijacking brain systems that regulate stress and reward, including neuropeptide Y (NPY) and corticotropin-releasing factor (CRF). The central actions of NPY and CRF have opposing functions in the regulation of emotional and reward-seeking behaviors; thus, dysfunctional interactions between these peptidergic systems could be involved in the development of these pathologies. We used converging physiological, pharmacological and chemogenetic approaches to identify a precise neural mechanism in the bed nucleus of the stria terminalis (BNST), a limbic brain region involved in pathological reward and anxiety behaviors, underlying the interactions between NPY and CRF in the regulation of binge alcohol drinking in both mice and monkeys. We found that NPY Y1 receptor (Y1R) activation in the BNST suppressed binge alcohol drinking by enhancing inhibitory synaptic transmission specifically in CRF neurons via a previously unknown G i-mediated, PKA-dependent postsynaptic mechanism. Furthermore, chronic alcohol drinking led to persistent alterations in Y1R function in the BNST of both mice and monkeys, highlighting the enduring, conserved nature of this effect across mammalian species. Together, these data provide both a cellular locus and signaling framework for the development of new therapeutics for treatment of neuropsychiatric diseases, including alcohol use disorders.

    Original languageEnglish (US)
    Pages (from-to)545-552
    Number of pages8
    JournalNature Neuroscience
    Volume18
    Issue number4
    DOIs
    StatePublished - Apr 28 2015

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    Binge Drinking
    Neuropeptide Y
    Corticotropin-Releasing Hormone
    Amygdala
    Alcohol Drinking
    Septal Nuclei
    Reward
    Neurons
    Haplorhini
    Anxiety
    Pathology
    Brain
    Synaptic Transmission
    Alcoholism
    Public Health
    Alcohols
    Pharmacology

    ASJC Scopus subject areas

    • Neuroscience(all)

    Cite this

    Pleil, K. E., Rinker, J. A., Lowery-Gionta, E. G., Mazzone, C. M., McCall, N. M., Kendra, A. M., ... Kash, T. L. (2015). NPY signaling inhibits extended amygdala CRF neurons to suppress binge alcohol drinking. Nature Neuroscience, 18(4), 545-552. https://doi.org/10.1038/nn.3972

    NPY signaling inhibits extended amygdala CRF neurons to suppress binge alcohol drinking. / Pleil, Kristen E.; Rinker, Jennifer A.; Lowery-Gionta, Emily G.; Mazzone, Christopher M.; McCall, Nora M.; Kendra, Alexis M.; Olson, David P.; Lowell, Bradford B.; Grant, Kathleen (Kathy); Thiele, Todd E.; Kash, Thomas L.

    In: Nature Neuroscience, Vol. 18, No. 4, 28.04.2015, p. 545-552.

    Research output: Contribution to journalArticle

    Pleil, KE, Rinker, JA, Lowery-Gionta, EG, Mazzone, CM, McCall, NM, Kendra, AM, Olson, DP, Lowell, BB, Grant, KK, Thiele, TE & Kash, TL 2015, 'NPY signaling inhibits extended amygdala CRF neurons to suppress binge alcohol drinking', Nature Neuroscience, vol. 18, no. 4, pp. 545-552. https://doi.org/10.1038/nn.3972
    Pleil KE, Rinker JA, Lowery-Gionta EG, Mazzone CM, McCall NM, Kendra AM et al. NPY signaling inhibits extended amygdala CRF neurons to suppress binge alcohol drinking. Nature Neuroscience. 2015 Apr 28;18(4):545-552. https://doi.org/10.1038/nn.3972
    Pleil, Kristen E. ; Rinker, Jennifer A. ; Lowery-Gionta, Emily G. ; Mazzone, Christopher M. ; McCall, Nora M. ; Kendra, Alexis M. ; Olson, David P. ; Lowell, Bradford B. ; Grant, Kathleen (Kathy) ; Thiele, Todd E. ; Kash, Thomas L. / NPY signaling inhibits extended amygdala CRF neurons to suppress binge alcohol drinking. In: Nature Neuroscience. 2015 ; Vol. 18, No. 4. pp. 545-552.
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