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。 There are some important sex differences in this addiction and its 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。 Using a newly developed 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）。

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.