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Interoceptive conditioning with nicotine: Changes in abuse liability

尼古丁的内感受调节：滥用倾向的变化

基本信息

批准号：
10406337
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
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-07-15 至 2024-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10406337
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 abuse liability 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

项目摘要

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。对个人而言，长期吸烟与随着心脏病和多种癌症的显著增加，即使是非烟草使用者的健康也受到影响。受到二手烟的负面影响。在这种成瘾性及其影响因素中，健康后果。女性平均比男性需要更少的时间成为尼古丁依赖，尝试戒烟，戒断时间较短，复发率较高，从尼古丁中获益较少替代疗法显然，个人和社会的巨大收益将来自更好的了解导致尼古丁依赖的因素。与药物有关的环境刺激例如尼古丁可以是寻求药物行为的强有力的调节剂。另一个重要因素是尼古丁依赖的发展和坚韧是尼古丁作为一种内感受性（内部）刺激进入与其他刺激/非条件的条件性关联刺激[US（同伴接受，酒精，工作休息，缓解压力）]。因此，随着时间的推移，吸烟者会出现有机会通过尼古丁的刺激作用发展丰富的食欲调节史。该获取的强化值可能有助于尼古丁成瘾的顽固性。使用新开发的创新性地将内感受性调节与尼古丁自我给药相结合的临床前动物模型，本申请将严格地检验以下假设尼古丁的条件作用历史，尼古丁刺激将获得条件强化值，加剧了尼古丁摄入行为的持续性。为此，具体目标将研究如何药物摄入的增强随尼古丁刺激的显著性（剂量）而变化（目的1），评估协同作用通过使用乙醇或蔗糖-乙醇溶液，在尼古丁和乙醇之间进行比较（目标2），并实施一种创新的消除方案，旨在削弱尼古丁的后天条件强化价值，在雌性和雄性大鼠中，目标刺激（目标3）的简单非强化程度更大。

项目成果

期刊论文数量（12）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Female rats display higher methamphetamine-primed reinstatement and c-Fos immunoreactivity than male rats.

DOI：
10.1016/j.pbb.2020.173089
发表时间：
2021-03
期刊：
PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR
影响因子：
3.6
作者：
Pittenger, Steven T.;Chou, Shinnyi;Murawski, Nathen J.;Barrett, Scott T.;Loh, Olivia;Duque, Juan F.;Li, Ming;Bevins, Rick A.
通讯作者：
Bevins, Rick A.

Reward-enhancing effects of d-amphetamine and its interactions with nicotine were greater in female rats and persisted across schedules of reinforcement.