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 尼古丁是烟草中主要的成瘾成分。对于个人而言，长期吸烟与 心脏病和多种癌症的发病率显着增加。研究人员越来越多地记录 与吸食含有尼古丁的调味电子烟油相关的健康问题。有一些重要的性 长期使用尼古丁的差异及其健康后果。平均而言，女性受到的影响更大 环境和社会文化因素，需要更少的时间来产生尼古丁依赖，更少的尝试 戒烟、戒烟时间较短、复发率较高、从尼古丁替代疗法中获益较少。巨大的 个人和社会的收益将来自于对影响因素的更全面的理解 尼古丁的使用和滥用。通过巴甫洛夫调节过程，环境刺激与 尼古丁等药物可以成为药物寻求行为的强大调节剂。另一个相关的和 尼古丁长期使用的一个重要因素是尼古丁的药理作用 一种内部（内感受）刺激，与其他强化物（例如同伴 接受、酒精、工作休息、缓解压力等）。因此，随着时间的推移，吸烟者/电子烟使用者会发展出丰富的内感受 调节历史与尼古丁的刺激作用。我们的长期目标是了解如何 条件反射历史改变了个体使用和误用的轨迹，并在此过程中提供了新的线索 如何改进戒烟计划。为此，我们最近开发了一种利用大鼠的创新方法 它将静脉注射（IV）尼古丁的内感受调节与随后的自我给药相结合。当IV 尼古丁反复与食欲增强剂（即蔗糖）配对，这种调节历史剂量和性别 依赖性地增加尼古丁的自我施用量（21％至126％）——这种效应在雌性大鼠中更为深远。 利用这种新方法的方法论优势，我们在本提案中实现了三个目标。 目标 1 将评估在保留间隔后回忆学习内容的需要是否会改变记忆的强度 尼古丁的条件强化作用。目标 2 将确定是否在过程中添加弱强化物 自我给药与尼古丁及其新获得的条件强化作用相互作用。目标3将 检查外部（外感受）刺激是否会与内感受尼古丁刺激竞争 条件强化值，从而削弱其对尼古丁摄入的后期影响。基本的理解 对影响尼古丁内感受调节效果的因素的研究将完善和推进我们的研究 理论模型。这些进展将为其他基础科学家提供基础研究和线索 面向致力于改进尼古丁使用障碍治疗方法的临床科学家和医疗保健提供者。