Effects of nicotine on dependence-related associative learning processes

尼古丁对依赖相关联想学习过程的影响

• 批准号: 9037633
• 负责人: Britta Hahn
• 金额: $ 7.6万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-04-01 至 2018-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9037633
• 关键词: Accounting; Adaptive Behaviors; Animals; Association Learning; Back; Behavior; Behavior Control; Behavior Therapy; Cause of Death; Crossover Design; Cues; Data; Dependence; Disease; Double-Blind Method; Equilibrium; Future; Health; Human; Lead; Learning; Maintenance; Medical; Nicotine; Nicotine Dependence; Outcome; Participant; Performance; Pharmaceutical Preparations; Pharmacological Treatment; Placebos; Play; Population; Prevalence; Process; Productivity; Resistance; Response to stimulus physiology; Role; Schedule; Smoker; Smoking; Smoking Behavior; Societies; Stimulus; Synaptic plasticity; Task Performances; Testing; Time; Tobacco Dependence; Tobacco smoking; Tobacco use; cigarette smoking; classical conditioning; computerized; conditioning; cost; design; drug of abuse; effective therapy; flexibility; indexing; learning extinction; nicotine abuse; non-smoker; novel; response; success; theories; treatment strategy; years of life lost

DESCRIPTION (provided by applicant): Tobacco smoking is among the two most common preventable causes of death in the US and world- wide, and causes enormous cost to society. The continued substantial prevalence of dependent tobacco consumption and poor quit success may reflect our incomplete understanding of the nicotine dependence process. Non-pharmacological factors, such as the behavioral control exerted by internal and external drug- associated stimuli, appear to play a dominant role in nicotine dependence, more than for any other drug of abuse. Nicotine's direct effects on synaptic plasticity and associative learning may facilitate the conditioning of smoking-associated stimuli and lead to stronger, more enduring cue control over behavior. However, such theories have not been backed by direct experimental evidence in humans. of the pro- posed study is that nicotine facilitates the incidental formation o stimulus-stimulus (S-S) and stimulus- response (S-R) associations and strengthens their resistance to context-adaptive modulation. This mechanism may promote a shift towards an automatic mode of nicotine-seeking largely controlled by conditioned cues. In 3 test sessions, 34 healthy non-smokers will perform computerized tasks in which incidental S-S and S-R associations impair flexible task-adaptive performance. In the first 2 sessions, scheduled with 2 intermediate days, a nicotine (7 mg/24 hrs) or placebo patch will be administered double-blind, in a counter- balanced sequence. In each of these patch sessions, each task paradigm will employ a unique stimulus set, Hypothesis 1 allowing direct comparison of the strength of incidental associations formed in the presence of nicotine or placebo . In test session 3, scheduled one week after the second patch session, participants perform shortened versions of the tasks, once with each of the two stimulus sets, to assess the persistence of associations formed in the presence of nicotine or placebo. This will test Hypothesis 2 that the presence of nicotine during the formation of S-S and S-R associations slows their decay over time. The demonstration that nicotine promotes conditioning mechanisms in humans that could promote automatized drug-taking behavior at the expense of flexible, context-adaptive behavior would lay the groundwork for comprehensive studies aimed at demonstrating the contribution of such mechanisms to dependent tobacco consumption. A broadened, data-backed view of nicotine dependence as a disorder of drug-induced maladaptive associative learning would provide a strong scientific rationale for developing and expanding behavioral and pharmacological treatment approaches aimed at breaking over-learned stimulus-contingent behavior and promoting flexible, context-adaptive control. The present proposal constitutes the necessary first step towards substantiating theories of a specific mechanism that may mark the nicotine dependence process and explain the paradoxically high abuse potential of nicotine. Results consistent with this theoretical account would motivate studies that may lead to more effective treatments of one of the most costly disorders to society.

描述(申请人提供)：吸烟是美国和世界范围内最常见的两种可预防的死亡原因之一，并造成巨大的社会成本。持续大量的烟草依赖消费和糟糕的戒烟成功可能反映了我们对尼古丁依赖过程的不完全理解。非药理学因素，如内部和外部药物相关刺激施加的行为控制，似乎在尼古丁依赖中发挥主导作用，比任何其他滥用药物更重要。尼古丁对突触可塑性和联想学习的直接影响可能会促进吸烟相关刺激的条件反射，并导致对行为的更强、更持久的线索控制。然而，这样的理论并没有在人体上得到直接实验证据的支持。尼古丁促进了刺激-刺激(S-S)和刺激-反应(S-R)联想的附带形成，并增强了它们对语境适应性调节的抵抗力。这种机制可能会促使人们转向一种在很大程度上受条件性暗示控制的自动寻找尼古丁模式。在3个测试阶段中，34名健康的非吸烟者将执行计算机化任务，其中偶然出现的S-S和S-R联想会损害灵活的任务适应能力。在前两个疗程中，计划在两个中间天，尼古丁(7毫克/24小时)或安慰剂贴片将按平衡顺序双盲给予。在每个贴片过程中，每个任务范例都将使用一个独特的刺激集，假设1允许直接比较在尼古丁或安慰剂存在时形成的附带联想的强度。在计划于第二次贴片治疗后一周进行的测试3中，参与者分别对两个刺激集执行一次任务的缩短版本，以评估在尼古丁或安慰剂存在的情况下形成的联系的持久性。这将检验假设2，即在S-S和S-R联想形成期间尼古丁的存在会随着时间的推移减缓它们的衰退。尼古丁促进了人类的条件反射机制，这种机制可能会促进自动化的吸毒行为，但代价是灵活的、上下文适应的行为，这一证明将为旨在证明这种机制对依赖烟草消费的贡献的全面研究奠定基础。将尼古丁依赖视为一种药物诱导的适应不良联想学习障碍的宽泛的、有数据支持的观点，将为开发和扩大旨在打破过度学习的刺激反应行为并促进灵活的、上下文适应的控制的行为和药物治疗方法提供强有力的科学依据。目前的提案是朝着证实特定机制的理论迈出的必要的第一步，该机制可能标志着尼古丁依赖过程，并解释尼古丁的高滥用潜力。与这一理论描述一致的结果将激励研究，可能导致对社会代价最高的疾病之一进行更有效的治疗。