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

Nat Commun. 2021 Nov 26;12(1):6945. doi: 10.1038/s41467-021-27268-7.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Animal / drug effects
  • Behavior, Animal / physiology
  • Dopamine / metabolism
  • Dopaminergic Neurons / drug effects
  • Dopaminergic Neurons / metabolism
  • Exploratory Behavior / drug effects*
  • Exploratory Behavior / physiology
  • Male
  • Mesencephalon / cytology
  • Mesencephalon / drug effects*
  • Mesencephalon / metabolism
  • Mice
  • Models, Animal
  • Nicotine / administration & dosage
  • Nicotine / adverse effects*
  • Optogenetics
  • Prejudice
  • Reward
  • Self Administration
  • Stereotaxic Techniques

Substances

  • Nicotine
  • Dopamine