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.

不良儿童经历（ACE）已与增加烟草使用的风险增加有关其他物质使用障碍。特别是，ACE数量较高的个体更多可能吸烟，在早期吸烟，进展到较重的吸烟，有较高的依赖性水平，不太可能退出。但是，人类实验室很少已经进行了研究，以检查ACE与吸烟风险之间的相互作用，以及这些关联的基础机制知之甚少。基于几个融合的证据线，我们提出了一个翻译框架，其中Aces是与导致失调奖励失调的皮质纹状体电路的改变有关加工，这反过尼古丁。拟议的研究将采用最初的尼古丁暴露实验室模型鼻喷雾以检查年轻人的主观反应和尼古丁的增强作用成人非吸烟者（n = 150）的ac症史介于0到4或更多。参与者会首先填写旨在评估中左右反应性的功能性神经影像学方案货币奖励，前额叶抑制性控制和皮质纹状体功能连通性。将评估对0，.5或1 mg剂量的尼古丁鼻喷雾的主观反应三个独立的固定剂量访问。然后，我们将评估尼古丁在选择会话。通常，我们假设增加对ACE的接触将与尼古丁的阳性主观和增强作用更大，皮质纹状体缺陷电路将介导ACE和尼古丁反应之间的关联，这是妇女中的协会将更加强大。这些结果将提供来自动物模型表明了早期生活压力对神经生物学途径的后果与成瘾有关。此外，这项工作将有助于解释吸烟的风险增加在暴露于ACE的个体中，将对预防和治疗有影响在这个高风险人口及以后吸烟。