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Inactivation of a CRF-dependent amygdalofugal pathway reverses addiction-like behaviors in alcohol-dependent rats

Author

Listed:
  • Giordano de Guglielmo

    (The Scripps Research Institute)

  • Marsida Kallupi

    (The Scripps Research Institute)

  • Matthew B. Pomrenze

    (The University of Texas at Austin)

  • Elena Crawford

    (The Scripps Research Institute)

  • Sierra Simpson

    (The Scripps Research Institute)

  • Paul Schweitzer

    (The Scripps Research Institute)

  • George F. Koob

    (National Institutes of Health)

  • Robert O. Messing

    (The University of Texas at Austin)

  • Olivier George

    (The Scripps Research Institute)

Abstract

The activation of a neuronal ensemble in the central nucleus of the amygdala (CeA) during alcohol withdrawal has been hypothesized to induce high levels of alcohol drinking in dependent rats. In the present study we describe that the CeA neuronal ensemble that is activated by withdrawal from chronic alcohol exposure contains ~80% corticotropin-releasing factor (CRF) neurons and that the optogenetic inactivation of these CeA CRF+ neurons prevents recruitment of the neuronal ensemble, decreases the escalation of alcohol drinking, and decreases the intensity of somatic signs of withdrawal. Optogenetic dissection of the downstream neuronal pathways demonstrates that the reversal of addiction-like behaviors is observed after the inhibition of CeA CRF projections to the bed nucleus of the stria terminalis (BNST) and that inhibition of the CRFCeA-BNST pathway is mediated by inhibition of the CRF-CRF1 system and inhibition of BNST cell firing. These results suggest that the CRFCeA-BNST pathway could be targeted for the treatment of excessive drinking in alcohol use disorder.

Suggested Citation

  • Giordano de Guglielmo & Marsida Kallupi & Matthew B. Pomrenze & Elena Crawford & Sierra Simpson & Paul Schweitzer & George F. Koob & Robert O. Messing & Olivier George, 2019. "Inactivation of a CRF-dependent amygdalofugal pathway reverses addiction-like behaviors in alcohol-dependent rats," Nature Communications, Nature, vol. 10(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-09183-0
    DOI: 10.1038/s41467-019-09183-0
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    Cited by:

    1. Matthew T. Birnie & Annabel K. Short & Gregory B. Carvalho & Lara Taniguchi & Benjamin G. Gunn & Aidan L. Pham & Christy A. Itoga & Xiangmin Xu & Lulu Y. Chen & Stephen V. Mahler & Yuncai Chen & Talli, 2023. "Stress-induced plasticity of a CRH/GABA projection disrupts reward behaviors in mice," Nature Communications, Nature, vol. 14(1), pages 1-10, December.

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