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Increased CRF signalling in a ventral tegmental area-interpeduncular nucleus-medial habenula circuit induces anxiety during nicotine withdrawal

Author

Listed:
  • Rubing Zhao-Shea

    (Brudnick Neuropsychiatric Research Institute, University of Massachusetts Medical School)

  • Steven R. DeGroot

    (Brudnick Neuropsychiatric Research Institute, University of Massachusetts Medical School)

  • Liwang Liu

    (Brudnick Neuropsychiatric Research Institute, University of Massachusetts Medical School)

  • Markus Vallaster

    (University of Massachusetts Medical School)

  • Xueyan Pang

    (Brudnick Neuropsychiatric Research Institute, University of Massachusetts Medical School)

  • Qin Su

    (University of Massachusetts Medical School)

  • Guangping Gao

    (University of Massachusetts Medical School)

  • Oliver J. Rando

    (University of Massachusetts Medical School)

  • Gilles E. Martin

    (Brudnick Neuropsychiatric Research Institute, University of Massachusetts Medical School)

  • Olivier George

    (Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute)

  • Paul D. Gardner

    (Brudnick Neuropsychiatric Research Institute, University of Massachusetts Medical School)

  • Andrew R. Tapper

    (Brudnick Neuropsychiatric Research Institute, University of Massachusetts Medical School)

Abstract

Increased anxiety is a prominent withdrawal symptom in abstinent smokers, yet the neuroanatomical and molecular bases underlying it are unclear. Here we show that withdrawal-induced anxiety increases activity of neurons in the interpeduncular intermediate (IPI), a subregion of the interpeduncular nucleus (IPN). IPI activation during nicotine withdrawal was mediated by increased corticotropin releasing factor (CRF) receptor-1 expression and signalling, which modulated glutamatergic input from the medial habenula (MHb). Pharmacological blockade of IPN CRF1 receptors or optogenetic silencing of MHb input reduced IPI activation and alleviated withdrawal-induced anxiety; whereas IPN CRF infusion in mice increased anxiety. We identified a mesointerpeduncular circuit, consisting of ventral tegmental area (VTA) dopaminergic neurons projecting to the IPN, as a potential source of CRF. Knockdown of CRF synthesis in the VTA prevented IPI activation and anxiety during nicotine withdrawal. These data indicate that increased CRF receptor signalling within a VTA–IPN–MHb circuit triggers anxiety during nicotine withdrawal.

Suggested Citation

  • Rubing Zhao-Shea & Steven R. DeGroot & Liwang Liu & Markus Vallaster & Xueyan Pang & Qin Su & Guangping Gao & Oliver J. Rando & Gilles E. Martin & Olivier George & Paul D. Gardner & Andrew R. Tapper, 2015. "Increased CRF signalling in a ventral tegmental area-interpeduncular nucleus-medial habenula circuit induces anxiety during nicotine withdrawal," Nature Communications, Nature, vol. 6(1), pages 1-14, November.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms7770
    DOI: 10.1038/ncomms7770
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    Cited by:

    1. Raquel Francés & Yasmine Rabah & Thomas Preat & Pierre-Yves Plaçais, 2024. "Diverting glial glycolytic flux towards neurons is a memory-relevant role of Drosophila CRH-like signalling," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

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