Circadian misalignment and reward function: a novel pathway to substance use

昼夜节律失调和奖励功能：物质使用的新途径

• 批准号: 8507192
• 负责人: Brant P. Hasler
• 金额: $ 15.54万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-15 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8507192
• 关键词: Acute; Adolescence; Adolescent; Adult; Alcohol or Other Drugs use; Anhedonia; Area; Behavior; Brain; Circadian Rhythms; Cross-Sectional Studies; Data; Development; Ensure; Environment; Esthesia; Etiology; Exhibits; Face; Foundations; Functional Magnetic Resonance Imaging; Goals; Hour; Human; Individual; Individual Differences; Intervention; Lead; Light; Link; Measures; Medial; Mediating; Melatonin; Mentored Research Scientist Development Award; Methodology; Methods; Modeling; Motivation; Neurobiology; Outcome; Pathway interactions; Patient Self-Report; Persons; Phase; Play; Prefrontal Cortex; Prevention; Preventive; Proxy; Recording of previous events; Recruitment Activity; Regulation; Relative (related person); Research; Research Personnel; Rewards; Risk; Risk-Taking; Role; Sampling; Scanning; Schedule; Schools; Simulate; Sleep; Solid; Staging; Substance Addiction; Substance Use Disorder; System; Testing; Time; Training; Translating; Ventral Striatum; addiction; adolescent substance use; binge drinking; design; discounting; disorder risk; early onset substance use; experience; follow-up; innovation; neural circuit; neurobehavioral; neuroimaging; novel; programs; prospective; research study; response; reward processing; skills; time use

DESCRIPTION (provided by applicant): The candidate's long-term goal is to develop an independent research program investigating the role of circadian rhythm disturbance and impaired reward function as mechanisms of vulnerability to substance use disorders (SUDs). Evidence suggests that circadian rhythms may play a key role in substance use (SU), specifically via interactions with the reward system. However, human studies have not yet examined the precise underlying mechanisms of these relationships. Thus, two priorities are (1) investigating the neurobehavioral underpinnings of circadian-reward interactions, and (2) clarifying how these circadian-reward mechanisms may contribute to SUD risk. Adolescence is a key developmental stage in which to investigate these mechanisms, as it is a period of marked changes in circadian rhythms, reward function, and initiation of SU. Studying the neurobehavioral mechanisms by which circadian rhythms modulate reward functioning may lead to a better understanding of the etiology of adolescent SU and inform prevention and treatment efforts. The candidate has a strong background in circadian and sleep research, and needs additional training to develop mastery in SU research and neuroimaging methods. The proposed K01 Mentored Research Scientist Development Award would ensure the candidate's successful transition to an independent investigator by providing conceptual and methodological training in three key areas: (1) expertise in adolescent SU from a developmental perspective, (2) expertise in the neurobiology of SU with particular focus on models of altered reward function, and (3) expertise in fMRI methodology, analysis, and interpretation. These training aims are well-matched to the proposed research plan, which aims to investigate the neurobehavioral underpinnings of circadian-reward interactions, and to explore whether circadian-reward mechanisms contribute to risk for SUDs. These goals align with NIDA's 2010 Prevention Objectives of elucidating the neural circuitry underlying addiction, and clarifying how environment and development influence risk and protective factors for SUDs. The proposed research will investigate an adolescent sample in cross-sectional and experimental studies, using a novel within-person design and fMRI to probe the role of circadian rhythms in reward-related brain function. The aims are: (1) to assess cross-sectional associations between SU, SUD risk, and self-reported circadian-sleep timing; (2) to assess diurnal variation in reward-related brain activation; (3) to examine the effects of experimentally-induced, ecologically-valid circadian misalignment on reward-related brain activation; and (4) to gather preliminary data on whether misalignment-associated changes in reward-related brain activation are related to SUD vulnerability. The proposed K01 award will integrate the candidate's previous experience and new skill areas, thus providing him with a solid foundation to launch an innovative, independent research program aimed at investigating the neurobehavioral mechanisms linking SU, reward function, and circadian rhythms, with the ultimate goal of translating identified mechanisms into novel interventions.

描述（由申请人提供）：候选人的长期目标是开发一个独立的研究计划，调查昼夜节律紊乱和奖励功能受损作为物质使用障碍（SUD）脆弱性机制的作用。有证据表明，昼夜节律可能在物质使用（SU）中发挥关键作用，特别是通过与奖励系统的相互作用。然而，人类研究尚未研究这些关系的确切潜在机制。因此，两个优先事项是（1）调查昼夜节律-奖励相互作用的神经行为基础，以及（2）澄清这些昼夜节律-奖励机制如何有助于SUD风险。青春期是研究这些机制的关键发育阶段，因为它是昼夜节律，奖励功能和SU启动的显着变化的时期。研究昼夜节律调节奖赏功能的神经行为机制可能会更好地了解青少年SU的病因，并为预防和治疗工作提供信息。 候选人在昼夜节律和睡眠研究方面有很强的背景，需要额外的培训来掌握SU研究和神经成像方法。拟议的K 01指导研究科学家发展奖将通过在三个关键领域提供概念和方法培训，确保候选人成功过渡到独立调查员：（1）从发展的角度来看青少年SU的专业知识，（2）SU的神经生物学专业知识，特别关注改变奖励功能的模型，（3）功能磁共振成像方法学，分析，和解释。这些培训目标与拟议的研究计划非常匹配，该计划旨在调查昼夜节律-奖励相互作用的神经行为基础，并探索昼夜节律-奖励机制是否有助于SUD的风险。这些目标与NIDA的2010年预防目标一致，即阐明成瘾的神经回路，并阐明环境和发展如何影响SUD的风险和保护因素。 拟议的研究将在横断面和实验研究中调查青少年样本，使用新颖的人内设计和fMRI来探索昼夜节律在奖励相关脑功能中的作用。其目标是：（1）评估SU、SUD风险和自我报告的昼夜睡眠时间之间的横截面关联;（2）评估奖励相关脑激活的昼夜变化;（3）检查实验诱导的、生态有效的昼夜节律失调对奖励相关脑激活的影响;以及（4）收集初步数据，以确定与奖励相关的大脑激活中的错误行为相关变化是否与SUD脆弱性相关。拟议的K 01奖将整合候选人以前的经验和新的技能领域，从而为他提供一个坚实的基础，以启动一个创新的，独立的研究计划，旨在调查神经行为机制连接SU，奖励功能和昼夜节律，最终目标是将确定的机制转化为新的干预措施。