Adolescence: A Sensitive Period for Nicotine Addiction

青春期：尼古丁成瘾的敏感期

• 批准号: 7048534
• 负责人: EDWARD D LEVIN
• 金额: $ 22.56万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-04-01 至 2009-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7048534
• 关键词: adolescence (12-20); age difference; behavior test; behavioral /social science research tag; cocaine; disease /disorder model; disease /disorder onset; drug addiction; gender difference; immature animal; laboratory rat; mature animal; nicotine; nicotine replacement; nonhuman therapy evaluation; pharmacokinetics; self medication; substance abuse related behavior; tobacco abuse

DESCRIPTION (provided by applicant): The great majority of tobacco addiction begins during adolescence, but very little is known about the neurobehavioral effects of nicotine in adolescents compared to adults. Adolescents are still undergoing important neurodevelopmental changes on the path to adulthood. Nicotine exposure in adolescence may have lasting impacts on this late neurodevelopment. There are suggestions in the clinical literature that more heavily addicted smokers begin smoking earlier in adolescence, but the impact of nicotine self-administration during adolescence versus self-selection bias whereby people more prone to heavy addiction also begin earlier, cannot be ethically unconfounded in humans. This project is based on our hypothesis beginning nicotine self-administration during adolescence leads to greater nicotine intake and dependence than beginning in adulthood. Our preliminary data demonstrated in the rat model of nicotine self-administration that rats with adolescent-onset nicotine self-administration self-administer substantially higher total doses of nicotine than adult-onset rats, This higher rate of nicotine self-administration continues into adulthood with an approximate doubling of nicotine self-administration. The proposed experiments will determine the causal relationship between adolescent-onset nicotine self-administration and enhanced long-term nicotine self-administration with these Specific Aims. 1. Determine the pharmacokinetics and dose-effect functions of nicotine in adolescents and adult rats. 2. Determine the impact of nicotine replacement and nicotinic antagonist therapy on nicotine self-administration in adolescent-onset and adult-onset nicotine self-administration. 3. Determine the age threshold for the adult-like nicotine self-administration. 4. Determine if adolescent-onset nicotine self-administration enhances cocaine dependence. 5. Determine sex differences in adolescent-onset nicotine self-administration. Nicotine pharmacokinetic measurements in adolescent and adult rats will be used to determine the effect of altered distribution and metabolism versus pharmacodynamic factors in accounting for age-related differences in nicotine self-administration. Benefits of this research include a more relevant animal model of adolescent-onset smoking, improved understanding of how adolescent-onset nicotine use potentiates nicotine intake, a cause and effect determination of the gateway hypothesis of adolescent nicotine use leading to harder drugs and the development of better treatments for adolescent-onset nicotine dependence.

描述（由申请人提供）：绝大多数烟草成瘾始于青春期，但与成年人相比，尼古丁对青少年神经行为的影响知之甚少。青少年在走向成年的道路上仍在经历重要的神经发育变化。青少年时期接触尼古丁可能会对后期神经发育产生持久的影响。在临床文献中有建议说，更多的严重成瘾的吸烟者在青春期开始吸烟的时间更早，但青春期尼古丁自我服用与自我选择偏见的影响，即更容易上瘾的人也更早开始吸烟，在人类身上不能在道德上没有混淆。这个项目是基于我们的假设，在青春期开始尼古丁自我服用会导致比成年期开始更多的尼古丁摄入和依赖。我们的初步数据表明，在尼古丁自我给药的大鼠模型中，青春期开始的尼古丁自我给药的大鼠比成年开始的大鼠自我给药的尼古丁总剂量高得多，这种较高的尼古丁自我给药率持续到成年，大约是尼古丁自我给药的两倍。