Prolonged nicotine exposure reduces aversion to the drug in mice by altering nicotinic transmission in the interpeduncular nucleus - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue eLife Année : 2023

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

Sarah Mondoloni
Claire Nguyen
Eléonore Vicq
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Maria Ciscato
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Joachim Jehl
Romain Durand-de Cuttoli
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Nicolas Torquet
Stefania Tolu
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Stéphanie Pons
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Uwe Maskos
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Fabio Marti
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Philippe Faure
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Alexandre Mourot
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Résumé

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 β4-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.
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Dates et versions

hal-04299318 , version 1 (22-11-2023)

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Sarah Mondoloni, Claire Nguyen, Eléonore Vicq, Maria Ciscato, Joachim Jehl, et al.. Prolonged nicotine exposure reduces aversion to the drug in mice by altering nicotinic transmission in the interpeduncular nucleus. eLife, 2023, 12, ⟨10.7554/eLife.80767⟩. ⟨hal-04299318⟩
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