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 烟草是高度添加的和dospite的提高对吸烟不利影响的认识 每天成千上万的青少年开始尝试香烟。其中约三分之二的过渡 从偶尔到日常吸烟到发展尼古丁成瘾。该研究计划的长期目标 是确定减少烟草中的尼古丁含量是否会阻止过渡到每日吸烟和 青少年尼古丁成瘾的发展。减少烟草中的尼古丁含量已经 提议作为减少吸烟的另一种方法。实际上，临床研究表明成年人 尼古丁成瘾吸烟比传统的高烟碱香烟少烟。这是， 但是，不知道青少年在吸烟时是否不太可能发展尼古丁成瘾 香烟。出于道德原因，无法比较低和高云素的增强特性 青少年中的香烟。我们研究的目的是确定积极的和负面的增强 与高烟碱香烟相比，低云蛋白香烟的特性降低了。积极 尼古丁的增强作用对于开始吸烟和负面增强作用至关重要 提取阻止人们维持禁欲。我们将使用已建立的大鼠烟草-smoke 暴露程序，以研究低，中间和高烟碱香烟的增强特性。 基于我们以前的尼古丁和烟草烟雾暴露研究，可以假设存在阳性 烟草的尼古丁含量与香烟的增强特性之间的关系。三个目标 建议检验这一假设。 1）确定烟草的尼古丁含量是否影响奖励 青春期雄性和雌性大鼠烟雾的特性。青春大鼠将用于研究奖励 烟草烟的影响是因为人们在青少年期间开始吸烟，这是一个增强的时期 开发尼古丁成瘾的脆弱性。 2）确定是否有不同的烟草烟雾 早期至中期期间的尼古丁水平会影响尼古丁摄入的获取和自我的动机 在雄性和雌性大鼠的青少年晚期治疗尼古丁。 3）确定尼古丁含量是否 烟草会影响青少年和成年初期尼古丁依赖性的发展， 女性。人们在青少年期间开始吸烟，并试图在成年期间戒烟。 因此，将在年轻的成年大鼠中调查戒断 青少年。可以预测，降低烟草中的尼古丁含量将降低阳性和 卷烟的负增强特性。因此，降低烟草中的尼古丁含量会 减少文明对社会的燃烧，因为更少的青少年过渡到日常吸烟和开发 尼古丁成瘾。这些研究将为FDA的监管机构提供有关降低有效性的信息 烟草中的尼古丁含量是防止过渡到日常吸烟和尼古丁成瘾的措施。