Transient nicotine exposure in early adolescent male mice freezes their dopamine circuits in an immature state

• Published in: Nature communications Vol. 15; no. 1; pp. 9017 - 19
• Main Authors: Reynolds, Lauren M., Gulmez, Aylin, Fayad, Sophie L., Campos, Renan Costa, Rigoni, Daiana, Nguyen, Claire, Le Borgne, Tinaïg, Topilko, Thomas, Rajot, Domitille, Franco, Clara, Fernandez, Sebastian P., Marti, Fabio, Heck, Nicolas, Mourot, Alexandre, Renier, Nicolas, Barik, Jacques, Faure, Philippe
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 18.10.2024; Nature Publishing Group; Nature Portfolio
• Subjects: 631/378/1689/5; 631/378/1788; 631/378/3920; 64; 64/60; 9/74; Addictions; Adolescents; Animals; Behavior, Animal - drug effects; Child development; Circuits; Development Biology; Dopamine; Dopamine - metabolism; Dopamine receptors; Dopaminergic Neurons - drug effects; Dopaminergic Neurons - metabolism; Embryology and Organogenesis; Exposure; Functional morphology; Humanities and Social Sciences; Life Sciences; Male; Males; Mice; Mice, Inbred C57BL; multidisciplinary; Neural networks; Neurobiology; Neurons and Cognition; Nicotine; Nicotine - pharmacology; Physiological responses; Science; Science (multidisciplinary); Toxicology
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-024-53327-w

How nicotine acts on developing neurocircuitry in adolescence to promote later addiction vulnerability remains largely unknown, but may hold the key for informing more effective intervention efforts. We found transient nicotine exposure in early adolescent (PND 21-28) male mice was sufficient to produce a marked vulnerability to nicotine in adulthood (PND 60 + ), associated with disrupted functional connectivity in dopaminergic circuits. These mice showed persistent adolescent-like behavioral and physiological responses to nicotine, suggesting that nicotine exposure in adolescence prolongs an immature, imbalanced state in the function of these circuits. Chemogenetically resetting the balance between the underlying dopamine circuits unmasked the mature behavioral response to acute nicotine in adolescent-exposed mice. Together, our results suggest that the perseverance of a developmental imbalance between dopamine pathways may alter vulnerability profiles for later dopamine-dependent psychopathologies. How nicotine impacts the adolescent development of neural circuitry is not fully understood. Here authors show that early adolescent nicotine exposure in male mice blocked the maturation of nicotine-evoked dopamine signaling, causing an immature, vulnerable behavioral response in adult mice. Restoring their adult-like nicotine-evoked signaling unmasks a mature behavioral response in male mice.