Pharmacological interventions to diminish nicotine associated responding

减少尼古丁相关反应的药物干预

• 批准号: 8862441
• 负责人: Rick A Bevins
• 金额: $ 28.57万
• 依托单位: UNIVERSITY OF NEBRASKA LINCOLN
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-06-01 至 2016-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8862441
• 关键词: Absence of pain sensation; Accounting; Address; Affect; Alcohols; Alkaloids; Appetitive Behavior; Area; Attention; Awareness; Back; Behavior; Biological; Bupropion; Chantix; Chronic; Cigarette; Complex; Conditioned Reflex; Cues; Data; Development; Disease; Drug Addiction; Drug usage; Elements; Environmental Tobacco Smoke; Event; Exposure to; Extinction (Psychology); Food; Goals; Grant; Health; Heart Diseases; Individual; Intervention; Lead; Learning; Ligands; Literature; Malignant Neoplasms; Methods; Minor; Modeling; Nature; Nicotine; Nicotine Dependence; Pharmaceutical Preparations; Pharmacotherapy; Pharyngeal structure; Physiological; Pre-Clinical Model; Process; Psychopathology; Publishing; Rattus; Recording of previous events; Research; Research Personnel; Rewards; Role; Series; Societies; Stimulus; Stress; Sucrose; Tobacco; Tobacco use; Work; Zyban; addiction; classical conditioning; conditioning; economic cost; interest; irritation; learning extinction; nornicotine; novel strategies; peer; programs; reinforcer; research study; response; smoking cessation; theories; varenicline

DESCRIPTION (provided by applicant): 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. The potential benefits to the individual and society that would come from a better understanding of the factors that contribute to nicotine dependence are enormous. Conditioning is one important factor that contributes to the addiction cycle. Research and theory on drug conditioning most often treats nicotine as an unconditioned stimulus or reinforcer that enters into an association with other stimuli (cigarette, situational cues) that reliably co-occur with its physiological effects. An understudied area that is also important for the development and tenacity of nicotine dependence is the ability of the pharmacological effects of nicotine to serve as an interoceptive stimulus for other reinforcing events (peer acceptance, alcohol, work breaks, stress relief, etc.). Indeed, there has been a recent rise in investigators' and practitioners' awareness of the role of interoceptive conditionin to a wide range of psychopathologies and diseases-including addiction. We have developed a preclinical model to study interoceptive conditioning with nicotine. Rats that have an appetitive learning history with nicotine will show evidence of conditioning controlled by the nicotine stimulus; that is, anticipatory food-seeking. The most provocative finding to date is that conditioning to the nicotine stimulus can be weakened by repeated non- reinforced presentation of an alternative drug (i.e., extinction) that shares interoceptive stimulus effects with nicotine. This "transfer of extinction" has been seen with varenicline (the smoking cessation aid Chantix(R)), bupropion (the smoking cessation aid Zyban(R)), and nornicotine (a potential smoking cessation aid that is a metabolite of nicotine and minor alkaloid in tobacco). The proposed research will build programmatically on this exciting finding by more closely examining novel approaches to deepening transfer of extinction, hence diminishing the control of nicotine over acquired appetitive behavior. In doing so, the experiments in this application introduce new methods for studying interoceptive stimuli to the field, begin to fill a significant gap in the scientific literature, advance our understanding of extinction processes involving nicotine, and elucidate the nature of the nicotine stimulus and treatment-relevant ligands.

描述（由申请人提供）：长期吸烟与心脏病和多种癌症的显着增加有关；即使是不吸烟的人的健康也会受到二手烟的负面影响。更好地了解导致尼古丁依赖的因素对个人和社会的潜在好处是巨大的。调节是导致成瘾周期的重要因素之一。药物调节的研究和理论通常将尼古丁视为一种无条件刺激或强化剂，它与其他刺激（香烟、情境线索）产生关联，这些刺激与其生理效应可靠地同时发生。对于尼古丁依赖的发展和持久性也很重要的一个尚未研究的领域是尼古丁的药理作用作为其他强化事件（同伴接受、酒精、工作休息、压力缓解等）的内感受刺激的能力。事实上，最近研究者和从业者越来越意识到内感受调节在包括成瘾在内的各种精神病理学和疾病中的作用。我们开发了一个临床前模型来研究尼古丁的内感受调节。具有尼古丁食欲学习历史的老鼠将表现出尼古丁刺激控制条件反射的证据；也就是说，预期性的食物寻找。迄今为止最具启发性的发现是，对尼古丁刺激的调节可以通过重复非强化地呈现与尼古丁共享内感受刺激作用的替代药物（即消退）来削弱。 这种“消退转移”已在伐尼克兰（戒烟辅助剂 Chantix(R)）、安非他酮（戒烟辅助剂 Zyban(R)）和去甲尼古丁（一种潜在的戒烟辅助剂，是尼古丁和次要的代谢物）中观察到。烟草中的生物碱）。拟议的研究将以这一令人兴奋的发现为基础，通过更仔细地研究加深灭绝转移的新方法，从而减少尼古丁对后天食欲行为的控制。在此过程中，本申请中的实验引入了研究内感受刺激的新方法，开始填补科学文献中的重大空白，增进我们对涉及尼古丁的消退过程的理解，并阐明尼古丁刺激和治疗的本质-相关配体。