Neurobehavioral mechanisms linking childhood adversity to increased risk for smoking

将童年不幸与吸烟风险增加联系起来的神经行为机制

基本信息

批准号：
10670365
负责人：
Maggie M Sweitzer
金额：
$ 56.47万
依托单位：
DUKE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-08-01 至 2027-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10670365
关键词：
21 year old Accounting Adolescent Adult Age Animal Model Behavioral Behavioral Mechanisms Behavioral Paradigm Brain Cigarette Corpus striatum structure Dependence Dopamine Dose Exposure to Functional Magnetic Resonance Imaging Functional disorder Goals Health Household Human Individual Individual Differences Intranasal Administration Laboratories Laboratory Study Lead Link Literature Measures Mediating Methods Modeling Neurobiology Nicotine Nicotine Nasal Spray Nose Outcome Participant Pathway interactions Physiological Placebos Prevention Procedures Process Protocols documentation Psychological reinforcement Reaction Recording of previous events Research Rewards Risk Role Severities Sex Differences Smoker Smoking Smoking treatment Socioeconomic Status Stress Substance Use Disorder Testing Time Tobacco use Translations Visit Woman Work addiction adverse childhood events childhood adversity cigarette smoke cognitive control depressive symptoms design drug of abuse early life adversity early life stress experience high risk population insight men neglect neurobehavioral neuroimaging neuromechanism nicotine exposure nicotine use non-smoker non-smoking preference prospective response reward anticipation reward processing sex smoking exposure smoking initiation translational framework young adult

项目摘要

Adverse childhood experiences (ACEs) have been linked to increased risk of tobacco use and other substance use disorders. In particular, individuals with a higher number of ACEs are more likely to smoke cigarettes, initiate smoking at earlier ages, progress to heavier smoking, have higher levels of dependence, and are less likely to quit. However, very few human laboratory studies have been conducted to examine interactions between ACEs and risk for smoking, and the mechanisms underlying these associations are poorly understood. Based on several converging lines of evidence, we propose a translational framework in which ACEs are associated with alterations in corticostriatal circuitry contributing to dysregulated reward processing, which in turn increases sensitivity to reinforcing effects of drugs of abuse, including nicotine. The proposed research will apply a laboratory model of initial nicotine exposure using nasal spray to examine subjective reactions and reinforcing effects of nicotine among young adult non-smokers (n=150) with a history of ACEs ranging from 0 to 4 or more. Participants will first complete a functional neuroimaging protocol designed to assess mesolimbic reactivity to monetary reward, prefrontal inhibitory control, and corticostriatal functional connectivity. Subjective reactions to 0, .5, or 1 mg doses of nicotine nasal spray will be assessed during three separate fixed-dose visits. We will then evaluate reinforcing effects of nicotine during a choice session. In general, we hypothesize that increased exposure to ACEs will be associated with greater positive subjective and reinforcing effects of nicotine, that deficits in corticostriatal circuitry will mediate the association between ACEs and nicotine reactions, and that this association will be stronger among women. These results will provide a critical translation from animal models demonstrating consequences of early life stress on neurobiological pathways relevant to addiction. Moreover, this work will help to explain the increased risk for smoking among individuals exposed to ACEs and will have implications for prevention and treatment of smoking in this high-risk population and beyond.

不良童年经历 (ACE) 与吸烟和吸烟风险增加有关其他物质使用障碍。特别是，拥有较多 ACE 数量的个体可能吸烟、较早开始吸烟、逐渐吸烟较多、有依赖性程度较高，戒烟的可能性较小。然而，人类实验室很少已经进行了研究来检查 ACE 与吸烟风险之间的相互作用，并且人们对这些关联背后的机制知之甚少。基于几个汇集证据线，我们提出了一个翻译框架，其中 ACE 是与导致奖赏失调的皮质纹状体回路的改变有关处理，这反过来又增加了对滥用药物强化效应的敏感性，包括尼古丁。拟议的研究将应用初始尼古丁暴露的实验室模型，使用鼻喷雾剂检查年轻人对尼古丁的主观反应和强化作用具有 0 至 4 或更多 ACE 病史的成年非吸烟者 (n=150)。参与者将首先完成旨在评估中脑边缘反应性的功能性神经影像方案金钱奖励、前额叶抑制控制和皮质纹状体功能连接。将在使用期间评估对 0、0.5 或 1 毫克剂量尼古丁鼻喷雾剂的主观反应三次单独的固定剂量就诊。然后我们将评估尼古丁在治疗过程中的增强作用选择会议。一般来说，我们假设 ACE 暴露的增加与随着尼古丁更大的积极主观和增强作用，皮质纹状体的缺陷电路将介导 ACE 和尼古丁反应之间的关联，并且该电路将介导 ACE 和尼古丁反应之间的关联妇女之间的联系将会更加牢固。这些结果将提供重要的翻译动物模型展示了早期生活压力对神经生物学途径的影响与成瘾有关。此外，这项工作将有助于解释吸烟风险增加的原因暴露于 ACE 的个体中，将对预防和治疗产生影响在这个高危人群及其他人群中吸烟。