Nicotine Self-Administration: Tobacco Pharmacotherapies

尼古丁自我给药：烟草药物疗法

基本信息

批准号：
7647355
负责人：
MATTHEW I PALMATIER
金额：
$ 18.27万
依托单位：
KANSAS STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-07-01 至 2011-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7647355
关键词：
Abstinence Affect Anhedonia Animal Model Animals Behavior Behavioral Brain Bupropion Chronic Disease Clinical Conflict (Psychology)Cues Data Development Drug Delivery Systems Enhancers Event Future Goals Human Incentives Infusion procedures Intervention Intravenous Laboratories Laboratory Animals Left Literature Maintenance Masks Modeling Motivation Neurobiology Nicotine Nicotine Dependence Outcome Pharmaceutical Preparations Pharmacotherapy Pre-Clinical Model Process Property Psychological reinforcement Research Rewards Risk Schedule Self Administration Sensory Smoke Smoker Smoking Smoking Behavior Smoking Cessation Intervention Stimulus Study Section Testing Tobacco Tobacco Dependence Tobacco use Withholding Treatment base design drug reinforcement insight meetings model design mortality neurobiological mechanism nicotine patch novel pre-clinical public health relevance reinforcer research study response sensory stimulus smoking cessation success synergism treatment strategy varenicline visual stimulus

项目摘要

DESCRIPTION (provided by applicant): Models of intravenous nicotine self-administration in laboratory animals are being used to investigate the behavioral and neurobiological consequences of nicotine reinforcement, and to aid in the development of novel pharmacotherapies for smoking cessation. Central to these models is the principle of primary reinforcement, which posits that response-contingent presentation of a primary reinforcer, nicotine, engenders robust operant behavior, whereas response-independent drug delivery does not. This dictum of nicotine as a primary reinforcer has been widely used to explain why people smoke tobacco - smoking results in the rapid delivery of nicotine to the brain, setting up a cascade of neurobiological processes that strengthen subsequent smoking behavior. However, there is mounting evidence that the primary reinforcement model of NIC self-administration fails to fully explain existing data from both the animal self- administration and human smoking literatures. We have recently proposed a "dual reinforcement" model designed to more fully capture the relationship between nicotine and self-administration, including smoking. The "dual reinforcement" model posits that nicotine acts as both a primary reinforcer and a reinforcement enhancer. Thus, self-administration (and smoking) is sustained by three actions: 1) nicotine, acting as a primary reinforcer, can sustain behavior that leads to its delivery; 2) nicotine, acting as a primary reinforcer, can establish neutral environmental stimuli as conditioned reinforcers through Pavlovian associations; and 3) nicotine, acting as a reinforcement enhancer, can magnify the incentive value of accompanying stimuli, including nicotine-associated conditioned reinforcers. The experiment proposed below extend the testing of a model that is sensitive to both the primary reinforcing and reinforcement enhancing effects of nicotine, focusing on questions regarding the potential mechanisms by which pharmacotherapeutic interventions for smoking cessation may reduce nicotine-seeking or replace the reinforcement enhancing effects of nicotine. These questions, the answers to which will result in a much more powerful model to explore the neurobiological mechanisms of nicotine addiction and to design better smoking cessation strategies, are: (1) Do pharmacotherapeutic interventions for smoking cessation share reinforcement enhancing effects with nicotine? (2) How do pharmacotherapeutic interventions with/without reinforcement enhancing properties affect primary reinforcement by nicotine in a paradigm that can isolate this effect? The answers to these questions will establish preliminary basis for future questions about how these pharmacotherapies may affect stimuli associated with the primary reinforcing effects of nicotine. PUBLIC HEALTH RELEVANCE: By promoting smoking behavior, nicotine dependence increases the risk of chronic disease and mortality. Our research, which employs an animal model of nicotine use, indicates that nicotine strengthens smoking behavior because nicotine is itself rewarding and because it also makes more rewarding other aspects of smoking, including environmental stimuli associated with the behavior. The experiments proposed will continue to test this model with the long term goal of establishing its usefulness in identifying the neurobiological basis of nicotine's actions and in the development of more effective smoking cessation aids.

描述（由申请人提供）：实验室动物中静脉注射尼古丁自我给药的模型被用来研究尼古丁增强的行为和神经生物学后果，并帮助开发新型的戒烟药物治疗。这些模型的核心是主要加固的原理，该原理认为主要增强剂，尼古丁，尼古丁，产生了强大的操作行为，而与反应无关的药物递送则没有。这种尼古丁作为主要钢筋的格言已被广泛用来解释为什么人们吸烟 - 吸烟会导致尼古丁迅速传递到大脑，从而建立了一系列神经生物学过程，从而增强了随后的吸烟行为。但是，有越来越多的证据表明，NIC自我管理的主要加强模型无法完全解释动物自我管理和人类吸烟文献的现有数据。我们最近提出了一个“双重加固”模型，旨在更充分地捕获尼古丁与自我管理之间的关系，包括吸烟。 “双重加固”模型认为，尼古丁既是主要的增强剂又是增强剂。因此，自我管理（和吸烟）由三个动作维持：1）尼古丁作为主要的增强剂，可以维持导致其传递的行为； 2）尼古丁作为主要的增强剂，可以通过帕夫洛维亚的关联来建立中性的环境刺激作为条件增强剂； 3）尼古丁充当增强剂增强剂，可以放大伴随刺激的激励价值，包括尼古丁相关的条件增强剂。下面提出的实验扩展了对主要加强和增强尼古丁的敏感的模型的测试，重点介绍了有关戒烟的药物治疗干预措施的潜在机制的问题，可以减少寻求尼古丁的尼古丁或替代尼古丁的增强作用。这些问题，将导致更强大的模型的答案，以探索尼古丁成瘾的神经生物学机制并设计更好的戒烟策略，是：（1）（1）是否有药物治疗性干预戒烟的药物治疗干预措施是否可以与尼古丁相同？（2）具有/没有加强特性的药物治疗干预措施如何影响尼古丁在可以隔离这种效果的范式中的一级增强？这些问题的答案将为以后的问题建立初步基础，以了解这些药物治疗如何影响与尼古丁的主要增强作用相关的刺激。公共卫生相关性：通过促进吸烟行为，尼古丁依赖性增加了慢性疾病和死亡率的风险。我们的研究采用了一种尼古丁使用动物模型，表明尼古丁可以增强吸烟行为，因为尼古丁本身是有益的，并且因为它也使吸烟的其他方面更有益，包括与行为相关的环境刺激。提出的实验将继续测试该模型，其长期目标是确定其在识别尼古丁行动的神经生物学基础和开发更有效的戒烟辅助工具方面的有用性。

项目成果

期刊论文数量（4）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Effects of nicotine on olfactogustatory incentives: preference, palatability, and operant choice tests.

尼古丁对嗅觉刺激的影响：偏好、适口性和操作选择测试。

DOI：
10.1093/ntr/ntt016
发表时间：
2013
期刊：
Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco
影响因子：
0
作者：
Palmatier,MatthewI;Lantz,JadenE;O'Brien,LauraC;Metz,SarahP
通讯作者：
Metz,SarahP