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

• Published in: Nature communications Vol. 12; no. 1; pp. 6945 - 15
• Main Authors: Dongelmans, Malou, Durand-de Cuttoli, Romain, Nguyen, Claire, Come, Maxime, Duranté, Etienne K., Lemoine, Damien, Brito, Raphaël, Ahmed Yahia, Tarek, Mondoloni, Sarah, Didienne, Steve, Bousseyrol, Elise, Hannesse, Bernadette, Reynolds, Lauren M., Torquet, Nicolas, Dalkara, Deniz, Marti, Fabio, Mourot, Alexandre, Naudé, Jérémie, Faure, Philippe
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 26.11.2021; Nature Publishing Group; Nature Portfolio
• Subjects: 631/378/116/2396; 631/378/1788; 631/378/3920; 9/30; Animals; Behavior, Animal - drug effects; Behavior, Animal - physiology; Decision analysis; Decision making; Dopamine; Dopamine - metabolism; Dopamine receptors; Dopaminergic Neurons - drug effects; Dopaminergic Neurons - metabolism; Exploitation; Exploration; Exploratory behavior; Exploratory Behavior - drug effects; Exploratory Behavior - physiology; Exposure; Genetics; Humanities and Social Sciences; Information processing; Intracranial self-stimulation; Life Sciences; Male; Mesencephalon; Mesencephalon - cytology; Mesencephalon - drug effects; Mesencephalon - metabolism; Mice; Models, Animal; multidisciplinary; Neurons; Neurons and Cognition; Nicotine; Nicotine - administration & dosage; Nicotine - adverse effects; Optics; Optogenetics; Phenotypes; Prejudice; Reinforcement; Reward; Science; Science (multidisciplinary); Self Administration; Self stimulation; Stereotaxic Techniques; Tradeoffs
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-021-27268-7

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. Chronic nicotine exposure impacts various components of decision-making processes, such as exploratory behaviors. Here, the authors identify the cellular mechanism and show that chronic nicotine exposure increases the tonic activity of VTA dopaminergic neurons and reduces exploration in mice.