1. Neuroscience

Prolonged nicotine exposure reduces aversion to the drug in mice by altering nicotinic transmission in the interpeduncular nucleus

  1. Sarah Mondoloni
  2. Claire Nguyen
  3. Eléonore Vicq
  4. Maria Ciscato
  5. Joachim Jehl
  6. Romain Durand-de Cuttoli
  7. Nicolas Torquet
  8. Stefania Tolu
  9. Stéphanie Pons
  10. Uwe Maskos
  11. Fabio Marti
  12. Philippe Faure  Is a corresponding author
  13. Alexandre Mourot  Is a corresponding author
  1. Sorbonne Université, INSERM, CNRS, France
  2. ESPCI Paris, France
  3. Institut Pasteur, France
https://doi.org/10.7554/eLife.80767
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Cite this article
  1. Sarah Mondoloni
  2. Claire Nguyen
  3. Eléonore Vicq
  4. Maria Ciscato
  5. Joachim Jehl
  6. Romain Durand-de Cuttoli
  7. Nicolas Torquet
  8. Stefania Tolu
  9. Stéphanie Pons
  10. Uwe Maskos
  11. Fabio Marti
  12. Philippe Faure
  13. Alexandre Mourot
(2023)
Prolonged nicotine exposure reduces aversion to the drug in mice by altering nicotinic transmission in the interpeduncular nucleus
eLife 12:e80767.
https://doi.org/10.7554/eLife.80767
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  3. Download .RIS

Abstract

Nicotine intake is likely to result from a balance between the rewarding and aversive properties of the drug, yet the individual differences in neural activity that control aversion to nicotine and their adaptation during the addiction process remain largely unknown. Using a two-bottle choice experiment, we observed considerable heterogeneity in nicotine-drinking profiles in isogenic adult male mice, with about half of the mice persisting in nicotine consumption even at high concentrations, whereas the other half stopped consuming. We found that nicotine intake was negatively correlated with nicotine-evoked currents in the interpeduncular nucleus (IPN), and that prolonged exposure to nicotine, by weakening this response, decreased aversion to the drug, and hence boosted consumption. Lastly, using knock-out mice and local gene re-expression, we identified b4-containing nicotinic acetylcholine receptors of IPN neurons as molecular and cellular correlates of nicotine aversion. Collectively, our results identify the IPN as a substrate for individual variabilities and adaptations in nicotine consumption.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files. Source data have been provided for all the figures.

Article and author information

Author details

  1. Sarah Mondoloni

    Neuroscience Paris Seine - Institut de Biologie Paris Seine, Sorbonne Université, INSERM, CNRS, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6134-3715

  2. Claire Nguyen

    Neuroscience Paris Seine - Institut de Biologie Paris Seine, Sorbonne Université, INSERM, CNRS, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0347-3626

  3. Eléonore Vicq

    Brain Plasticity Unit, ESPCI Paris, Paris, France
    Competing interests
    The authors declare that no competing interests exist.

  4. Maria Ciscato

    Brain Plasticity Unit, ESPCI Paris, Paris, France
    Competing interests
    The authors declare that no competing interests exist.

  5. Joachim Jehl

    Brain Plasticity Unit, ESPCI Paris, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9821-7619

  6. Romain Durand-de Cuttoli

    Neuroscience Paris Seine - Institut de Biologie Paris Seine, Sorbonne Université, INSERM, CNRS, Paris, France
    Competing interests
    The authors declare that no competing interests exist.

  7. Nicolas Torquet

    Neuroscience Paris Seine - Institut de Biologie Paris Seine, Sorbonne Université, INSERM, CNRS, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9032-193X

  8. Stefania Tolu

    Neuroscience Paris Seine - Institut de Biologie Paris Seine, Sorbonne Université, INSERM, CNRS, Paris, France
    Competing interests
    The authors declare that no competing interests exist.

  9. Stéphanie Pons

    Département de neuroscience, Institut Pasteur, Paris, France
    Competing interests
    The authors declare that no competing interests exist.

  10. Uwe Maskos

    Département de neuroscience, Institut Pasteur, Paris, France
    Competing interests
    The authors declare that no competing interests exist.

  11. Fabio Marti

    Neuroscience Paris Seine - Institut de Biologie Paris Seine, Sorbonne Université, INSERM, CNRS, Paris, France
    Competing interests
    The authors declare that no competing interests exist.

  12. Philippe Faure

    Neuroscience Paris Seine - Institut de Biologie Paris Seine, Sorbonne Université, INSERM, CNRS, Paris, France
    For correspondence
    phfaure@gmail.com
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3573-4971

  13. Alexandre Mourot

    Brain Plasticity Unit, ESPCI Paris, Paris, France
    For correspondence
    almourot@gmail.com
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8839-7481

Funding

Agence Nationale de la Recherche (ANR-21-CE16-0012 CHOLHAB)

  • Alexandre Mourot

Labex Biopsy

  • Claire Nguyen

Labex Memolife

  • Joachim Jehl

Labex Memolife

  • Alexandre Mourot

Agence Nationale de la Recherche (ANR-17-CE16-0016 SNP-NIC)

  • Philippe Faure

Fondation pour la Recherche Médicale (FRM EQU201903007961)

  • Philippe Faure

Institut National Du Cancer (TABAC-16-022)

  • Philippe Faure

Institut National Du Cancer (TABAC-19-02)

  • Philippe Faure

Institut National Du Cancer (SPA-21-002)

  • Philippe Faure

Fondation de France (Prix Médisite)

  • Alexandre Mourot

Fondation pour la Recherche Médicale (FDT201904008060)

  • Sarah Mondoloni

Fondation pour la Recherche Médicale (FDT20170437427)

  • Romain Durand-de Cuttoli

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All experiments were performed in accordance with the recommendations for animal experiments issued by the European Commission directives 219/1990, 220/1990 and 2010/63, and approved by Sorbonne Université.

Copyright

© 2023, Mondoloni et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Sarah Mondoloni
  2. Claire Nguyen
  3. Eléonore Vicq
  4. Maria Ciscato
  5. Joachim Jehl
  6. Romain Durand-de Cuttoli
  7. Nicolas Torquet
  8. Stefania Tolu
  9. Stéphanie Pons
  10. Uwe Maskos
  11. Fabio Marti
  12. Philippe Faure
  13. Alexandre Mourot
(2023)
Prolonged nicotine exposure reduces aversion to the drug in mice by altering nicotinic transmission in the interpeduncular nucleus
eLife 12:e80767.
https://doi.org/10.7554/eLife.80767

Share this article

https://doi.org/10.7554/eLife.80767

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