Tobacco: relationship between reduced nicotine content and reinforcement in rats

烟草：大鼠尼古丁含量降低与强化之间的关系

• 批准号: 9313227
• 负责人: Adriaan Willem Bruijnzeel
• 金额: $ 37.54万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-15 至 2019-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9313227
• 关键词: Abstinence; Adolescence; Adolescent; Adult; Affect; Affinity; Air; Awareness; Binding Sites; Brain; Cigarette; Clinical Research; Dependence; Development; Dose; Effectiveness; Electrodes; Ethics; Exposure to; FDA approved; Female; Female Adolescents; Goals; Health; Intake; Knowledge; Life; Male Adolescents; Measures; Modeling; Motivation; Negative Reinforcements; Nicotine; Nicotine Dependence; Nicotinic Receptors; Pattern; Positive Reinforcements; Probability; Procedures; Property; Psychological reinforcement; Rattus; Relapse; Research; Rewards; Self Stimulation; Self-Administered; Smoke; Smoker; Smoking; Societies; Testing; Tobacco; Tobacco smoke; Tobacco use; Training; Withdrawal; Withholding Treatment; authority; base; cigarette smoking; density; drug of abuse; drug relapse; emerging adult; environmental tobacco smoke exposure; experience; experimental study; high reward; male; median forebrain bundle; prevent; programs; smoking addiction; smoking cessation; young adult

SUMMARY Tobacco is highly addictive and despite increasing awareness about the adverse health effects of smoking each day thousands of adolescents start experimenting with cigarettes. About two-thirds of them transition from occasional to daily smoking and develop a nicotine addiction. The long-term goal of this research program is to determine if decreasing the nicotine content in tobacco will prevent the transition to daily smoking and the development of nicotine addiction in adolescents. Decreasing the nicotine content in tobacco has been proposed as an alternative approach to reduce smoking. Indeed, clinical studies indicate that adults with a nicotine addiction smoke fewer low-nicotine cigarettes than conventional high-nicotine cigarettes. It is, however, not known if adolescents are less likely to develop a nicotine addiction when they smoke low-nicotine cigarettes. For ethical reasons it is not possible to compare the reinforcing properties of low and high-nicotine cigarettes in adolescents. The objective of our studies is to determine if the positive and negative reinforcing properties of low-nicotine cigarettes are diminished compared to those of high-nicotine cigarettes. The positive reinforcing effects of nicotine are critical for the initiation of smoking and the negative reinforcing effects of withdrawal prevent people from maintaining abstinence. We will use an established rat tobacco-smoke exposure procedure to investigate the reinforcing properties of low, intermediate, and high-nicotine cigarettes. Based on our previous nicotine and tobacco smoke exposure studies, it is hypothesized that there is a positive relationship between the nicotine-content of tobacco and the reinforcing properties of cigarettes. Three aims are proposed to test this hypothesis. 1) Determine if the nicotine content of tobacco affects the rewarding properties of smoke in adolescent male and female rats. Adolescent rats will be used to study the rewarding effects of tobacco smoke because people start smoking during adolescence and this is a period of enhanced vulnerability for developing a nicotine addiction. 2) Determine if exposure to tobacco smoke with various nicotine levels during early- to mid-adolescence affects the acquisition of nicotine intake and the motivation to self- administer nicotine during late adolescence in male and female rats. 3) Determine if the nicotine content of tobacco affects the development of nicotine dependence during adolescence and early adulthood in males and females. People start smoking during adolescence and attempt to quit smoking during young adulthood. Therefore, withdrawal will be investigated in young adult rats in which smoke exposure was initiated during adolescence. It is predicted that lowering the nicotine content in tobacco will decrease the positive and negative reinforcing properties of cigarettes. Consequently, lowering the nicotine content in tobacco would decrease the burden of cigarettes on society as fewer adolescents transition to daily smoking and develop a nicotine addiction. These studies will inform the FDA’s regulatory authority about the effectiveness of reducing the nicotine content in tobacco as a measure to prevent the transition to daily smoking and nicotine addiction.

概括 烟草很容易上瘾，尽管人们越来越认识到吸烟对健康的不利影响 每天都有成千上万的青少年开始尝试吸烟。大约三分之二的人转型 从偶尔吸烟到每天吸烟并产生尼古丁成瘾。本研究计划的长期目标 是为了确定减少烟草中的尼古丁含量是否会阻止向日常吸烟的转变以及 青少年尼古丁成瘾的发展。降低烟草中的尼古丁含量 提议作为减少吸烟的替代方法。事实上，临床研究表明，患有以下疾病的成年人 尼古丁成瘾者吸的低尼古丁香烟比传统的高尼古丁香烟要少。这是， 然而，尚不清楚青少年在吸低尼古丁烟时是否不太可能出现尼古丁成瘾 香烟。出于道德原因，不可能比较低尼古丁和高尼古丁的增强特性 青少年吸烟。我们研究的目的是确定正强化和负强化是否 与高尼古丁香烟相比，低尼古丁香烟的特性有所减弱。积极的一面 尼古丁的强化作用对于开始吸烟至关重要，而尼古丁的负面强化作用则至关重要。 戒断会阻止人们保持禁欲。我们将使用一种既定的老鼠烟草烟 暴露程序来研究低、中、高尼古丁香烟的增强特性。 根据我们之前的尼古丁和烟草烟雾暴露研究，假设存在积极的影响 烟草的尼古丁含量与卷烟的增强性能之间的关系。三个目标 建议检验这一假设。 1) 确定烟草中的尼古丁含量是否影响奖励 青春期雄性和雌性大鼠的烟雾特性。青春期老鼠将被用来研究奖励 烟草烟雾的影响，因为人们在青春期开始吸烟，这是一个增强的时期 容易产生尼古丁成瘾。 2) 确定是否暴露于各种烟草烟雾中 青春期早期到中期的尼古丁水平会影响尼古丁摄入量的获得和自我学习的动机 在雄性和雌性大鼠青春期后期给予尼古丁。 3) 测定烟碱含量是否 烟草会影响男性和青少年在青春期和成年早期对尼古丁依赖的发展 女性。人们在青春期开始吸烟，并在成年初期尝试戒烟。 因此，将对年轻成年大鼠进行戒断研究，其中在吸烟期间开始暴露于烟雾中。 青春期。据预测，降低烟草中的尼古丁含量将降低积极和 香烟的负强化特性。因此，降低烟草中的尼古丁含量将 随着越来越少的青少年过渡到每天吸烟并养成习惯，减少香烟对社会的负担 尼古丁成瘾。这些研究将向 FDA 监管机构通报减少 烟草中的尼古丁含量作为防止向日常吸烟过渡和尼古丁成瘾的措施。