Individualistic reward-seeking strategies that predict response to nicotine emerge among isogenic male mice living in a micro-society

PLoS Biol. 2024 Oct 24;22(10):e3002850. doi: 10.1371/journal.pbio.3002850. eCollection 2024 Oct.

Abstract

Individual animals differ in their traits and preferences, which shape their social interactions, survival, and susceptibility to disease, including addiction. Nicotine use is highly heterogenous and has been linked to the expression of personality traits. Although these relationships are well documented, we have limited understanding of the neurophysiological mechanisms that give rise to distinct behavioral profiles and their connection to nicotine susceptibility. To address this question, we conducted a study using a semi-natural and social environment called "Souris-City" to observe the long-term behavior of individual male mice. Souris-City provided both a communal living area and a separate test area where mice engaged in a reward-seeking task isolated from their peers. Mice developed individualistic reward-seeking strategies when choosing between water and sucrose in the test compartment, which, in turn, predicted how they adapted to the introduction of nicotine as a reinforcer. Moreover, the profiles mice developed while isolated in the test area correlated with their behavior within the social environment, linking decision-making strategies to the expression of behavioral traits. Neurophysiological markers of adaptability within the dopamine system were apparent upon nicotine challenge and were associated with specific profiles. Our findings suggest that environmental adaptations influence behavioral traits and sensitivity to nicotine by acting on dopaminergic reactivity in the face of nicotine exposure, potentially contributing to addiction susceptibility. These results further emphasize the importance of understanding interindividual variability in behavior to gain insight into the mechanisms of decision-making and addiction.

MeSH terms

  • Animals
  • Behavior, Animal* / drug effects
  • Behavior, Animal* / physiology
  • Dopamine / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Nicotine* / pharmacology
  • Reward*
  • Social Behavior
  • Social Environment

Substances

  • Nicotine
  • Dopamine

Grants and funding

This work was supported by the Centre National de la Recherche Scientifique CNRS UMR 8246 and 8249, INSERM U1130, the Foundation for Medical Research (FRM https://www.frm.org/fr, Equipe FRM DEQ2013326488 to PF), the French National Cancer Institute (https://www.e-cancer.fr) and the French Institute for Public Health Research (IReSP) (https://iresp.net/en/presentation-english/) for Grant TABAC-16-01, TABAC-19-020, SPAV1-21-002 and SPAV1-23-005 (to PF), French state funds managed by the ANR (https://anr.fr/en/) for ANR-19-CE16-0028 Bavar to PF and NR). LMR was supported by a NIDA–Inserm Postdoctoral Drug Abuse Research Fellowship. Fourth-year PhD fellowship from Fondation pour la Recherche Médicale (FDT201904008060 to SM). Fourth-year PhD fellowship from the Biopsy Labex (CN). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.