Transient nicotine exposure in early adolescent male mice freezes their dopamine circuits in an immature state
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.
Authors
- Tinaïg Le Borgne (ORCID: https://orcid.org/0009-0007-9971-1935)
- Claire Nguyen (ORCID: https://orcid.org/0000-0002-0347-3626)
- Thomas Topilko (ORCID: https://orcid.org/0000-0002-3478-8591)
- Sebastián P. Fernández (ORCID: https://orcid.org/0000-0003-0683-5562)
- Lauren M. Reynolds (ORCID: https://orcid.org/0000-0003-3798-2055)
- Nicolas Renier (ORCID: https://orcid.org/0000-0003-2642-4402)
- Sophie L. Fayad (ORCID: https://orcid.org/0000-0002-4834-6524)
- Domitille Rajot
- Jacques Barik (ORCID: https://orcid.org/0000-0002-4276-0927)
- Alexandre Mourot (ORCID: https://orcid.org/0000-0002-8839-7481)
- Renan Costa Campos (ORCID: https://orcid.org/0000-0002-3166-2379)
- Clara Franco (ORCID: https://orcid.org/0000-0003-4927-3846)
- Daiana Rigoni (ORCID: https://orcid.org/0000-0002-4247-4330)
- Philippe Fauré (ORCID: https://orcid.org/0000-0003-3573-4971)
- Nicolas Heck (ORCID: https://orcid.org/0000-0002-5754-8873)
- Fabio Marti (ORCID: https://orcid.org/0000-0002-3604-457X)
- Aylin Gulmez (ORCID: https://orcid.org/0009-0002-1320-7062)
Institutions
- Centre National de la Recherche Scientifique (FR)
- Inserm (FR)
- Université Côte d'Azur (FR)
- Sorbonne Université (FR)
- Institut de Biologie Paris-Seine (FR)
- Institut du Cerveau (FR)
- Institut de Pharmacologie Moléculaire et Cellulaire (FR)
- Neurosciences Paris-Seine (FR)
- ESPCI Paris (FR)
Publication Details
- Journal
- Nature Communications
- Published
- 2024-10-18
- DOI
- https://doi.org/10.1038/s41467-024-53327-w
- Citations
- 5
- Primary Topic
- Nicotinic Acetylcholine Receptors Study
- Type
- article
- Field-Weighted Citation Impact
- 1.17
Funders
- Agence Nationale de la Recherche
- Institut National Du Cancer