Chronic nicotine increases midbrain dopamine neuron activity and biases individual strategies towards reduced exploration in mice

Nature Communications volume 12, Article number : 6945 (2021)

Malou Dongelmans, Romain Durand-de Cuttoli, Claire Nguyen, Maxime Come, Etienne K. Duranté, Damien Lemoine, Raphaël Brito, Tarek Ahmed Yahia, Sarah Mondoloni, Steve Didienne, Elise Bousseyrol, Bernadette Hannesse, Lauren M. Reynolds, Nicolas Torquet, Deniz Dalkara, Fabio Marti, Alexandre Mourot, Jérémie Naudé & Philippe Faure


Long-term exposure to nicotine alters brain circuits and induces profound changes in decision-making strategies, affecting behaviors both related and unrelated to drug seeking and consumption. Using an intracranial self-stimulation reward-based foraging task, we investigated in mice the impact of chronic nicotine on midbrain dopamine neuron activity and its consequence on the trade-off between exploitation and exploration. Model-based and archetypal analysis revealed substantial inter-individual variability in decision-making strategies, with mice passively exposed to nicotine shifting toward a more exploitative profile compared to non-exposed animals. We then mimicked the effect of chronic nicotine on the tonic activity of dopamine neurons using optogenetics, and found that photo-stimulated mice adopted a behavioral phenotype similar to that of mice exposed to chronic nicotine. Our results reveal a key role of tonic midbrain dopamine in the exploration/exploitation trade-off and highlight a potential mechanism by which nicotine affects the exploration/exploitation balance and decision-making.

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