Genetic influences impacting nicotine use and abuse during adolescence: Insights from human and rodent studies

Abstract

Nicotine use continues to be a major public health concern, with an alarming recent rise in electronic cigarette consumption. Heritability estimates of nicotine use and abuse range from 40% to 80%, providing strong evidence that genetic factors impact nicotine addiction-relevant phenotypes. Although nicotine use during adolescence is a key factor in the development of addiction, it remains unclear how genetic factors impact adolescent nicotine use and abuse. This review will discuss studies investigating genetic factors impacting nicotine use during adolescence. Evidence from both rodent and human studies will be summarized and integrated when possible. Human adolescent studies have largely included candidate gene studies for genes identified in adult populations, such as genes involved in nicotine metabolism, nicotinic acetylcholine receptor signaling, dopaminergic signaling, and other neurotransmitter signaling systems. Alternatively, rodent studies have largely taken a discovery-based approach identifying strain differences in adolescent nicotine addiction-relevant behaviors. Here, we aim to answer the following three questions by integrating human and rodent findings: (1) Are there genetic variants that uniquely impact nicotine use during adolescence? (2) Are there genetic variants that impact both adolescent and adult nicotine use? and (3) Do genetic factors in adolescence significantly impact long-term consequences of adolescent nicotine use? Determining answers for these three questions will be critical for the development of preventative measures and treatments for adolescent nicotine use and addiction.

Keywords: Adolescence; Animal models; Candidate gene; Cyp2a6; Dopamine; NAChR; Nicotine.

Figure 1.. Interacting factors contribute to nicotine abuse and addiction.

Ethnicity, genetics, sex, and adolescence interact to impact biological processes, which in turn impact responses to nicotine, which ultimately impact nicotine abuse and addiction. This review paper summarizes evidence for how genetic factors in gene subsets (nicotine metabolism, nAChRs, dopamine signaling, and other neurotransmitter systems impact nicotine addiction phenotypes, including reward, intake, and withdrawal, across adolescence.