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

Nature Communications 2024
Reynolds LM, Gulmez A, Fayad SL, Campos RC, Rigoni D, Nguyen C, Le Borgne T, Topilko T, Rajot D, Franco C, Marti F, Heck N, Mourot A, Renier N, Barik J, and Faure Ph.

Abstract

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.