Nicotine and Gene Expression in Adolescent Brain

描述（由申请人提供）：青春期是一个特别脆弱的发展时期，其特点是寻求新奇和冒险行为的增加。 虽然在青少年为成人世界的生活做准备时鼓励探索和实验是有益的，但这些行为也可能导致青少年人口中吸烟的高发病率。 由于大脑中对情绪调节和行为控制很重要的前额叶皮层等区域在这一时期继续发育，因此不成熟的大脑可能会导致青少年人群中的尼古丁成瘾问题。 由于在人类青少年中检查尼古丁成瘾的困难，啮齿动物模型已成为检查青少年对尼古丁反应的行为和分子基础的有力工具。 使用这个模型，我们已经开始确定青少年前额叶皮层中的基因，这些基因与急性尼古丁治疗后的成年人相比差异表达。 我们还发现，与成年人不同，青少年不适应尼古丁配对的环境。 该建议的重点是进一步研究参与前额叶皮层发育的分子底物，并确定尼古丁对这些底物的影响。 此外，还将研究压力对青少年尼古丁配对条件反射的影响。 深入了解青少年和成人大脑之间的分子和行为成分差异，以及了解这些差异如何与成瘾和渴望相关，可能会导致更有效的干预措施。

DESCRIPTION (provided by applicant): Adolescence is a particularly vulnerable period in development that is marked by an increase in novelty-seeking and risk-taking behaviors. Although beneficial in encouraging exploration and experimentation as adolescents prepare for life in an adult world, these behaviors may also contribute to the high incidence of smoking in the adolescent population. Since regions of the brain like the prefrontal cortex, which are important for emotional regulation and behavioral control, continue to develop throughout this period, it is likely that an immature brain contributes to the problem of nicotine addiction in the adolescent population. Because of the difficulty in examining nicotine addiction in human adolescents, the rodent model has become a powerful tool for examining the behavioral and molecular underpinnings of the adolescent response to nicotine. Using this model, we have begun to identify genes in the adolescent prefrontal cortex that are differentially expressed compared to the adult following acute nicotine treatment. We have also found that, unlike adults, adolescents do not condition to a nicotine-paired environment. The focus of this proposal is to further examine the molecular substrates involved in the development of the prefrontal cortex and to determine the influence of nicotine on these substrates. In addition, the influence of stress on nicotine-paired conditioning in adolescents will be performed. Insights into the molecular and behavioral components that differ between adolescent and adult brain, and an understanding of how these differences relate to addiction and craving, may lead to more effective interventions.