Examining the Behavioral and Molecular Aspects of Adolescent Nicotine Dependence: Implications for Vulnerability to Drugs of Abuse

摘要

Approximately 200 million men and 100 million women smoke worldwide. In the United States, an estimated 25.9 million men (23.9 percent) and 20.7 million women (18.1 percent) are smokers. The commencement of smoking at a young age is thought to increase addiction liability, decrease the probability of successful cessation, and correlate with a higher number of cigarettes smoked per day. Studies from the World Health Organization indicate that between 80,000 and 100,000 children start smoking every day worldwide. These statistics suggest that adolescence is a critical phase for developing nicotine dependence. The work in this dissertation contributes to the further understanding of this unique developmental period. Our research shows that various aspects of nicotine dependence are both age- and sex-dependent. We observed age- and sex-related differences in both nicotine reward and withdrawal models that imply a heightened vulnerability for adolescents. In addition, we have investigated possible behavioral and molecular mechanisms which may underlie the elevated vulnerability to dependence. The data illustrate that while behavioral mechanisms only play a minor role in the differences seen in reward and withdrawal, molecular mechanisms appear to have a greater contribution. Specifically, increased nicotinic receptor function is likely to be a substantial contributor to age-related disparities. In addition, nicotine is one of the first and most commonly abused drugs in adolescence and is known to be a strong predictor of subsequent alcohol and other drug abuse. Our research investigated the effects of adolescent nicotine exposure on both nicotine and cocaine dependence in adulthood. We found that exposure to nicotine during the early phase of adolescence affects both nicotine reward and withdrawal in adulthood. Moreover, this exposure also bears impact on other drugs of abuse such as cocaine. In summary, our data suggest that early adolescence is the most critical period for becoming dependent to nicotine and that early experimentation with nicotine may lead to enhanced vulnerability to dependence on more illicit drugs of abuse. It is imperative that we understand why adolescents have a heightened susceptibility to nicotine dependence so that better smoking cessation therapies and prevention messages can be developed for this age group.