Understanding and mitigating exacerbated nicotine use resulting from Pavlovianinteroceptive conditioning

了解和缓解巴甫洛夫内感受调节导致的尼古丁使用加剧

• 批准号: 10736191
• 负责人: Rick A Bevins
• 金额: $ 35.98万
• 依托单位: UNIVERSITY OF NEBRASKA LINCOLN
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-01 至 2028-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10736191
• 关键词: Address; Alcohols; Association Learning; Basic Science; Biological; Biology; Chronic; Clinical; Desire for food; Development; Dose; Environmental Risk Factor; Failure; Female; Foundations; Friends; Goals; Health; Health Personnel; Heart Diseases; Heart Rate; Incubated; Individual; Intake; Intravenous; Learning; Literature; Location; Malignant Neoplasms; Methodology; Nicotine; Nicotine Dependence; Nicotine Use Disorder; Outcome; Pharmaceutical Preparations; Pre-Clinical Model; Process; Rattus; Recording of previous events; Relapse; Research; Research Personnel; Rewards; Rodent; Role; Science; Scientific Advances and Accomplishments; Scientist; Self Administration; Sex Differences; Smell Perception; Smoker; Smoking; Societies; Stimulus; Stress; Sucrose; Taste Perception; Testing; Theoretical model; Time; Tobacco; Tobacco use; Translating; Woman; Work; combustible tobacco; conditioning; drug abstinence; drug seeking behavior; economic cost; electronic liquid; forgetting; improved; innovation; interest; male; men; nicotine cessation; nicotine replacement; nicotine self-administration; nicotine use; novel strategies; peer; pharmacologic; prevent; programs; reinforcer; sex; sociocultural determinant; vaper; vaping; visual stimulus

PROJECT ABSTRACT Nicotine is the primary addictive constituent in tobacco. For an individual, chronic tobacco use is associated with a significant increase in heart disease and many forms of cancer. Increasingly, researchers are documenting health issues associated with vaping flavored e-juice containing nicotine. There are some important sex differences in chronic nicotine use and its health consequences. Women on average are impacted more by environmental and sociocultural factors, take less time to become nicotine dependent, make fewer attempts to quit, abstain for less time, relapse at higher rates, and benefit less from nicotine replacement therapy. Enormous gains to the individual and society would come from a more complete understanding of factors that contribute to nicotine use and misuse. Through Pavlovian conditioning processes, environmental stimuli associated with drugs such as nicotine can become powerful modulators of drug-seeking behavior. Another related and important factor in the development of chronic nicotine use is the pharmacological effects of nicotine serving as an internal (interoceptive) stimulus that enters into a conditioned association with other reinforcers (e.g., peer acceptance, alcohol, work breaks, stress relief, etc.). Thus, smokers/vapers over time develop a rich interoceptive conditioning history with the stimulus effects of nicotine. Our long-term objective is to understand how this conditioning history alters the trajectory of use and misuse in individuals and, in doing so, provide new clues on how to improve cessation programs. To this end, we recently developed an innovative new approach using rats that merges interoceptive conditioning of intravenous (IV) nicotine with its later self-administration. When IV nicotine is repeatedly paired with an appetitive reinforcer (i.e., sucrose), this conditioning history dose- and sex- dependently increases nicotine self-administration (21 to 126%)—an effect more profound in female rats. Leveraging the methodological strengths of this new approach, we address three Aims in the present proposal. Aim 1 will assess whether the need to recall the learning after a retention interval alters the strength of the conditioned reinforcing effects of nicotine. Aim 2 will determine whether the addition of a weak reinforcer during self-administration interacts with nicotine and its newly acquired conditioned reinforcing effects. Aim 3 will examine whether an external (exteroceptive) stimulus will compete with the interoceptive nicotine stimulus for conditioned reinforcing value, thus weakening its later impact on nicotine intake. A fundamental understanding of such factors that influence the effect of interoceptive conditioning with nicotine will refine and advance our theoretical models. These advancements will provide foundational research for other basic scientists and clues for clinical scientists and healthcare providers working to improve approaches to treating nicotine use disorder.

项目摘要 尼古丁是烟草中的主要添加剂成分。对于个人，慢性烟草使用与 心脏病和多种形式的癌症的显着增加。研究人员越来越记录 与含有尼古丁的烟e-juice相关的健康问题。有一些重要的性 慢性尼古丁使用及其健康后果的差异。女性平均受到更多影响 环境和社会文化因素，花费更少的时间才能依赖尼古丁，而是尝试更少的尝试 退出，戒烟时间更少，以较高的速度退休，并从尼古丁替代疗法中受益较少。巨大的 获得个人和社会的收益将来自对贡献因素的完全理解 尼古丁的使用和滥用。通过帕夫洛维亚调节过程，与之相关的环境刺激 尼古丁等药物可以成为寻求毒品行为的强大调节剂。另一个相关和 慢性尼古丁使用开发的重要因素是尼古丁的药物作用 与其他增强剂进入条件缔合的内部（互感）刺激（例如 接受，酒精，工作中断，减轻压力等）。这是，随着时间的流逝，吸烟者/蒸气会发展出丰富的感受性 通过尼古丁的刺激作用来调节病史。我们的长期目标是了解如何 条件历史改变了个人的使用和错过的轨迹，并为此提供了新的线索 如何改善戒烟计划。为此，我们最近使用老鼠开发了一种创新的新方法 这将静脉内（IV）尼古丁的感受性调节与后来的自我管理。当iv时 尼古丁一再与食欲增强剂（即蔗糖）配对，这种调理史剂量和性别 - 依赖性地增加了尼古丁自我给药（21％至126％），这对雌性大鼠的影响更加深刻。 利用这种新方法的方法论优势，我们解决了本提案中的三个目标。 AIM 1将评估保留间隔后需要回忆学习的需要改变 尼古丁的条件增强作用。 AIM 2将确定是否在 自我管理与尼古丁及其新获得的条件增强作用相互作用。目标3意志 检查外部（外部感受）刺激是否会与互感的尼古丁刺激竞争 有条件的增强价值，从而削弱了其后来对尼古丁摄入的影响。基本的理解 这些因素影响与尼古丁互感调节作用的因素将完善并推进我们的 理论模型。这些进步将为其他基本科学家和集群提供基础研究 对于临床科学家和医疗保健提供者，致力于改善治疗尼古丁使用障碍的方法。