Starting to smoke at a young age is a risk factor for later dependence and use of other drugs. To understand why, a Parisian team is seeking to identify the biological mechanisms that are impacted by early smoking. She demonstrated, in mice, that exposure to nicotine during adolescence causes a freeze in the development of brain circuits. dopaminergicwhich persists into adulthood.
Cancers, cardiovascular and respiratory diseases… tobacco remains to this day the leading cause of avoidable mortality in France. Despite the implementation of numerous measures to combat smoking, nearly one in two adolescents had already tried tobacco in 2022. This is a major public health problem because smoking early is a risk factor for smoking. later and greater dependence throughout life. Early nicotine use has also been associated with an increased risk of anxiety disorders, depression, and problematic use of other drugs like alcohol.
Within the Paris Seine Neurosciences unit, Philippe Faure’s team attempted to translate these observations into biological realities. The researchers particularly studied the impact of nicotine on the development of dopaminergic brain circuits during adolescence. “ Cthe circuits, particularly involved in motivation and learning, are experiencing very significant growth and remodeling durant l’adolescence. The experiences lived during this period have a lasting influence their sensitivityexplains Philippe Faure. However, nicotine acts directly on the neurons that compose them. »
A maturing system
Previous work had highlighted the existence of two distinct dopaminergic subnetworks, which produce different responses in the event of stimulation by nicotine: the first causes a “reinforcing” effect, that is to say an increase in the appetite for this substance, while the second induces anxious behavior. “ These two answers are well described in adult mices,” clarifies Lauren Reynolds, post-doctoral student and first author of this work. To go further, the team carried out, again in mice, recordings of the activity of dopaminergic neurons in each of the two subnetworks, coupled with behavioral tests. In the event of first nicotine consumption in adulthood, the two subnetworks are equally activated. On the other hand, an imbalance is observed in adolescent animals: the activity of the network which causes the reinforcing effect predominates compared to that of the circuit involved in the anxiogenic effect. This means that young animals are very sensitive to the positive effect of nicotine. “ During the transition to adulthood, it operates as a rebalancing in the effect induced by nicotine on these two subnetworks “, explains Lauren Reynolds.
A broken balance
« But our observations indicate that early administration of nicotine reshuffles these cardswarns the scientist. If exposed during adolescence, the imbalance persists into adulthood. This means that the reinforcing effect – therefore the attraction for nicotine – remains more important than the anxiety-inducing effect. We can say that exposure to nicotine during adolescence freezes dopaminergic networks in an immature state. “, she summarizes. The team wishes to continue this work by exploring in particular the long-term behavioral consequences of this freezing of dopaminergic circuits, or the effect of other drugs on these circuits.
Lauren Reynolds is a postdoctoral researcher in the Neurophysiology and Behavior team co-directed by Philippe Faure and Alexandre Mourot, researcher Insermnow installed in the Brain Plasticity laboratory of the Higher School of Industrial Physics and Chemistry in the city of Paris.
Source : L. Reynolds et coll. Transient nicotine exposure in early adolescent male mice freezes their dopamine circuits in an immature state. Nat CommunOctober 18, 2024; DOI: 10.1038/s41467-024–53327‑w
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