Understanding how opioids affect the experiential and neural signatures of feelings of social connection with close others

项目摘要 拟议的项目是一名新的和早期的调查员提交的关于R01(PAR-19-384)的新申请。 与亲密的人建立社会联系是人类的基本需要。感觉与他人建立了可靠的联系 积极地预测健康和幸福，而消极地感觉与他人脱节或孤立 影响健康。然而，较少人了解的是，社会主观感受的过程 随着时间的推移，连接会一直保持。与历史悠久的动物模型一致，可以追溯到20世纪70年代的S， 最近在人类身上的实验研究表明，阿片类药物有助于与亲密朋友的社会联系， 浪漫的伴侣和家人。具体地说，纳曲酮，一种常见的药物处方，以帮助 从阻止自然产生的阿片类药物作用的成瘾中恢复，不幸的是导致减少 在对亲近的人的社交感方面，这是一个健康的样本。这些发现提高了 用于治疗成瘾的药物可能会给最严重的 长期维持的有效贡献者：密切的社会关系。的确，密切的社会关系 而这种关系中的“社会联系”的感觉是预防复发的主要因素 也是提高药物辅助治疗有效性的最有价值的工具之一。基于 这些发现，人们越来越感兴趣的是阿片类药物通路是否有助于社会感觉 以一种因果的方式与亲密的其他人联系，以及这些影响可能如何发生。然而，它仍然 令人惊讶的是，阿片类药物的社会心理后果及其对社会联系的贡献 还没有在人类身上得到更充分的探索。因此，这个项目的主要目标是进行一项 在人类中阐明阿片类药物在日常自然感觉中的因果作用的新实验操作 实验室外的社会联系，(2)社会联系感觉的神经信号，以及(3) 在与朋友和家人的个性化体验中使用社交关系的感觉 实验室任务标准化。为此，我们建议以210名年轻、健康的样本为目标 成人进行多方法随机安慰剂对照临床试验。其他探索性目标将审查 纳曲酮是否能引起日常社交感觉的改变预测神经的变化 对社会任务的反应，以及纳曲酮是否以不同方式影响女性的社会关系感觉 还有男人。该提案将把药理机制与脑功能的神经成像参数联系起来。 以及实验室外和实验室环境中的情感社交体验。因此，我们 预计这项研究将有助于对神经生物学途径的新的基础知识 维持社会联系对阿片成瘾治疗的影响。

Project Summary The proposed project is a new submission by a New and Early Stage Investigator for an R01 (PAR-19-384). Social connection with close others is a fundamental human need. Feeling connected to others reliably and robustly predicts health and wellbeing whereas feeling disconnected or isolated from others negatively impacts health. Less well understood, however, are the processes by which subjective feelings of social connection are maintained over time. Consistent with long-standing animal models dating back to the 1970’s, recent experimental work in humans has shown that opioids contribute to social connection with close friends, romantic partners, and family. Specifically, naltrexone, a common medication prescribed to assist in the recovery from addiction that blocks the action of naturally occurring opioids, unfortunately leads to a reduction in feelings of social connection toward close others in an otherwise healthy sample. These findings raise the possibility that the medication used to treat addiction may introduce an unintended barrier to one of the most effective contributors to long-term maintenance: close social relationships. Indeed, close social relationships and the feelings of ‘social connection’ within such relationships are major contributors to relapse prevention and one of the most valued tools for enhancing the effectiveness of medication-assisted treatment. Based on these findings, there has been a growing interest in whether opioid pathways contribute to feelings of social connection with close others in a causal manner and how these effects might occur. However, it remains surprising that the social psychological consequences of opioids and their contribution to social connection have not been more fully explored in humans. Therefore, the primary objective of this project is to conduct a novel experimental manipulation in humans to clarify the causal role of opioids in (1) daily, naturalistic feelings of social connection outside of the laboratory, (2) the neural signatures of feelings of social connection, and (3) feelings of social connection in response to personalized experiences with friends and family using standardized laboratory tasks. For these purposes, we propose targeting a sample of 210 young, healthy adults on a multi-method randomized placebo-controlled clinical trial. Additional exploratory aims will examine whether naltrexone induced changes in daily feelings of social connection predict variation in neural responding to social tasks, and whether naltrexone differently affects feelings of social connection in women and men. The proposal will link pharmacological mechanisms with neuroimaging parameters of brain function and affective social experience both outside of the laboratory and in the laboratory setting. We therefore anticipate that this study will contribute to new fundamental knowledge of the neurobiological pathways underlying the maintenance of social connection with implications for the treatment of opioid addiction.