Prolonged nicotine exposure reduces aversion to the drug in mice by altering nicotinic transmission in the interpeduncular nucleus
- Sorbonne Université, INSERM, CNRS, France
- ESPCI Paris, France
- Institut Pasteur, France
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
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.
Reviewing Editor
- Lan Ma, Fudan University, China
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.
Version history
- Preprint posted: December 17, 2021 (view preprint)
- Received: June 3, 2022
- Accepted: May 29, 2023
- Accepted Manuscript published: May 30, 2023 (version 1)
- Version of Record published: June 9, 2023 (version 2)
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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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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