Mechanisms underlying the enduring addiction vulnerability conferred by nicotine in adolescence

Onset of nicotine use in adolescence has been associated with an enduring risk of later addiction to nicotine or to other drugs of abuse, although the underlying mechanisms are not completely elucidated. While cigarette use in adolescence has declined over recent years, e-cigarette use has soared, highlighting a renewed need to understand the long-term consequences of adolescent nicotine use. This review examines clinical and preclinical evidence for an enduring addiction vulnerability following exposure to nicotine in adolescence, and integrates recent mechanistic studies that propose that this long-term vulnerability may be conferred by the actions of nicotine on multi-level developmental processes that shape dopaminergic circuitry in adolescence. These changes to the developmental trajectory of dopamine circuitry may, in turn, underpin an increased sensitivity to nicotine and other drugs later in life. Understanding these mechanisms informs harm reduction and intervention strategies, including pharmacological and behavioral approaches, to mitigate long-term addiction risks associated with adolescent nicotine use.