Interoceptive conditioning with nicotine: Changes in abuse liability

尼古丁的内感受调节：滥用倾向的变化

• 批准号: 10163151
• 负责人: Rick A Bevins
• 金额: $ 35.72万
• 依托单位: UNIVERSITY OF NEBRASKA LINCOLN
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-07-15 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10163151
• 关键词: Affect; Alcohol consumption; Alcohols; Animal Model; Area; Attention; Awareness; Behavior; Behavioral; Biological; Chronic; Cigarette; Desire for food; Development; Disease; Dose; Drug abuse; Ethanol; Extinction (Psychology); Female; Food; Goals; Health; Heart Diseases; Heart Rate; Individual; Intake; Interoception; Intravenous; Learning; Link; Literature; Malignant Neoplasms; Measures; Methods; Nicotine; Nicotine Dependence; Pharmaceutical Preparations; Pharmacology; Pre-Clinical Model; Process; Protocols documentation; Psychopathology; Rattus; Recording of previous events; Relapse; Research; Research Personnel; Risk; Role; Science; Scientific Advances and Accomplishments; Self Administration; Sex Differences; Sex Factors; Smoker; Smoking; Societies; Stimulus; Stress; Sucrose; Testing; Time; Tobacco; Tobacco use; Woman; Work; addiction; base; conditioning; design; drug seeking behavior; economic cost; enhancing factor; environmental tobacco smoke; improved outcome; innovation; male; men; negative affect; nicotine replacement; nicotine use; novel; peer; pre-clinical; programs; reinforcer; response; sex; smoking cessation; synergism; theories

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; even the health of non-tobacco users is negatively affected by second-hand smoke. There are some important sex differences in this addiction and its health consequences. Women on average take less time than men to become nicotine dependent, make fewer attempts to quit smoking, abstain for less time, relapse at higher rates, and benefit less from nicotine replacement therapy. Clearly, enormous gains to the individual and society would come from a better understanding of factors that contribute to nicotine dependence. Environmental stimuli associated with drugs such as nicotine can be powerful modulators of drug-seeking behavior. Another important factor to the development and tenacity of nicotine dependence is the pharmacological effects of nicotine serving as an interoceptive (internal) stimulus entering into a conditioned association with other reinforcers/unconditioned stimuli [USs (peer acceptance, alcohol, work breaks, stress relief)]. Consequently, over time, a smoker has an opportunity to develop a rich appetitive conditioning history with the stimulus effects of nicotine. This acquired reinforcing value likely contributes to the tenacity of the nicotine addiction. Using a newly developed preclinical animal model that innovatively merges interoceptive conditioning with nicotine self-administration, the present application will rigorously test the hypothesis that following an appetitive interoceptive conditioning history with nicotine, the nicotine stimulus will acquire conditioned reinforcing value that exacerbates the persistence of nicotine-taking behavior. To this end, the Specific Aims will examine how such enhancement of drug intake varies with the salience (dose) of the nicotine stimulus (Aim 1), assess the synergy between nicotine and ethanol by using ethanol or sucrose-ethanol solution as the US (Aim 2), and implement an innovative extinction protocol designed to weaken the acquired conditioned reinforcing value of nicotine to a greater extent than just simple non-reinforcement of the target stimulus (Aim 3) in female and male rats.

项目摘要 尼古丁是烟草中的主要成瘾成分。对于个人，慢性烟草使用是相关的 心脏病和多种形式的癌症显着增加；甚至非烟草用户的健康也是 受二手烟的负面影响。这种成瘾及其存在一些重要的性别差异 健康后果。女性平均比男性少花费时间依赖尼古丁的时间少 试图戒烟，戒烟更少的时间，以较高的速度复发，并从尼古丁中受益较少 替代疗法。显然，个人和社会的巨大收益将来自一个更好的 了解导致尼古丁依赖性的因素。与药物相关的环境刺激 例如尼古丁可以是寻求毒品行为的强大调节剂。另一个重要因素 尼古丁依赖性的发展和坚韧性是尼古丁作为一种药理作用 与其他增强剂/无条件的条件关联进入条件关联（内部）刺激（内部）刺激 刺激[USS（同伴接受，酒精，工作休息，减轻压力）]。因此，随着时间的流逝，吸烟者有一个 通过尼古丁的刺激作用，有机会发展丰富的食欲病史。这获得了 增强价值可能有助于尼古丁成瘾的坚韧。使用新开发 临床前动物模型，将互感条件与尼古丁自我管理合并， 本应用程序将严格检验以下情况的假设 尼古丁刺激以尼古丁的条件病史，将获得条件增强的价值 加剧了尼古丁的行为的持久性。为此，具体目标将研究如何 药物摄入量的增强随尼古丁刺激的显着性（AIM 1）而变化，评估协同作用 通过使用乙醇或蔗糖 - 乙醇溶液作为美国（AIM 2），并实施，在尼古丁和乙醇之间 一种创新的灭绝协议，旨在削弱尼古丁的获得的条件增强价值 在女性和男性大鼠中，不仅仅是对目标刺激的简单不强化（目标3）。