Sorbonne Université, Inserm, CNRS, Neuroscience Paris Seine - Institut de Biologie Paris Seine (NPS - IBPS), Paris, France
Eléonore Vicq
Sorbonne Université, Inserm, CNRS, Neuroscience Paris Seine - Institut de Biologie Paris Seine (NPS - IBPS), Paris, France; Brain Plasticity Unit, CNRS, ESPCI Paris, PSL Research University, Paris, France
Maria Ciscato
Brain Plasticity Unit, CNRS, ESPCI Paris, PSL Research University, Paris, France
Sorbonne Université, Inserm, CNRS, Neuroscience Paris Seine - Institut de Biologie Paris Seine (NPS - IBPS), Paris, France; Brain Plasticity Unit, CNRS, ESPCI Paris, PSL Research University, Paris, France
Romain Durand-de Cuttoli
Sorbonne Université, Inserm, CNRS, Neuroscience Paris Seine - Institut de Biologie Paris Seine (NPS - IBPS), Paris, France
Sorbonne Université, Inserm, CNRS, Neuroscience Paris Seine - Institut de Biologie Paris Seine (NPS - IBPS), Paris, France
Stefania Tolu
Sorbonne Université, Inserm, CNRS, Neuroscience Paris Seine - Institut de Biologie Paris Seine (NPS - IBPS), Paris, France
Stéphanie Pons
Institut Pasteur, Unité Neurobiologie intégrative des systèmes cholinergiques, Département de neuroscience, Paris, France
Uwe Maskos
Institut Pasteur, Unité Neurobiologie intégrative des systèmes cholinergiques, Département de neuroscience, Paris, France
Fabio Marti
Sorbonne Université, Inserm, CNRS, Neuroscience Paris Seine - Institut de Biologie Paris Seine (NPS - IBPS), Paris, France; Brain Plasticity Unit, CNRS, ESPCI Paris, PSL Research University, Paris, France
Sorbonne Université, Inserm, CNRS, Neuroscience Paris Seine - Institut de Biologie Paris Seine (NPS - IBPS), Paris, France; Brain Plasticity Unit, CNRS, ESPCI Paris, PSL Research University, Paris, France
Sorbonne Université, Inserm, CNRS, Neuroscience Paris Seine - Institut de Biologie Paris Seine (NPS - IBPS), Paris, France; Brain Plasticity Unit, CNRS, ESPCI Paris, PSL Research University, Paris, France
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.
