The mechanisms by which nicotine consumption in adolescence increases the risk of addiction in adulthood remain mysterious. In a recent study published in Nature Communicationsscientists, reveal that, in mouseexposure to the nicotine during this critical period lastingly disrupts the developing dopaminergic circuits, thus promoting a state of vulnerability prolonged.
Exposure to nicotine during adolescence has long been associated with an increased risk of addiction to the drug in adulthood. However, the precise mechanisms by which nicotine disrupts brain development and promotes this risk of addiction are still poorly understood. The study, published in the journal Nature Communicationssheds new light on this question.
Adolescent Mice Exposed to Nicotine Show Prolonged Vulnerability to Nicotine
The scientists first found that adolescent mice had increased sensitivity to the rewarding effects of nicotine, both physiologically and behaviorally. They then showed that mice exposed to nicotine during their early adolescence demonstrated, once adults, behaviors and physiological responses similar to those observed in young adolescent mice.
In other words, exposure to nicotine during adolescence seemed to freeze these animals in a prolonged state of vulnerability, characterized by increased sensitivity to the rewarding effects of nicotine and decreased responses to the anxiety-inducing effects of the substance. .
This phenomenon is linked to a disruption of the circuits involved in reward management.
Scientists have established that this phenomenon is linked to a disruption of the circuits synthesizing dopamineand neurotransmitter key in rewards management.
More specifically, nicotine affects two groups of dopaminergic neurons differently depending on their projections: neurons projecting to the nucleus accumbens, a central brain region involved in reinforcement and motivation, were particularly affected in adolescent mice, but also in adults who had used nicotine during adolescence.
Conversely, neurons projecting to the amygdala, a region playing a role in the management of emotions and fear, did not show comparable disturbances.
These results suggest that exposure to nicotine during this critical developmental period permanently imbalances dopamine circuits, thereby maintaining individuals in an immature brain state, and making them more likely to develop addiction as adults.
By restoring the balance of this dopaminergic neuronal activity, scientists were able to restore normal behavior in adult mice that had been exposed to nicotine during adolescence, demonstrating that targeted interventions aimed at restoring the activity of the dopaminergic circuit reward can reduce a learned vulnerability to drugs.
Adolescent mice show increased sensitivity to the rewarding effects of nicotine, while the negative emotional effects are less pronounced. Dopamine neurons projecting to the nucleus accumbens, a key region in the regulation of reward and motivation, display an amplified response to nicotine in adolescents compared to adults.
© Lauren Reynolds
On the other hand, the neurons projecting to the amygdala (in blue), involved in the management of emotions and fear, do not undergo any notable modification. Exposure to nicotine during adolescence maintains this neuronal imbalance in adults, thus prolonging the state of vulnerability to addiction.
References:
Reynolds, LM, Gulmez, A., Fayad, SL et al.
Transient nicotine exposure in early adolescent male mice freezes their dopamine circuits in an immature state.
Nat Common 159017 (2024). https://doi.org/10.1038/s41467-024-53327-w
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