Brain circuit, behavior and experience signatures of human drug-altered states

项目概要（项目4） 摇头丸（摇头丸）和氯胺酮是越来越受欢迎的滥用药物。相比于更 然而，传统兴奋剂对它们的作用方式、主观效果以及如何产生作用的了解较少。 这些效果促进了持续使用。我们的目标是整合自我报告，行为和神经措施， 详细描述摇头丸和氯胺酮的实时效应。这样我们就能 我们对药物改变的大脑状态如何引起急性药物体验和药物使用结果的理解。 我们将首先使用神经成像来绘制这些药物对人类体验的急性影响，重点是 解离性、情感性和奖励相关反应。其次，我们将探讨药物诱导的行为效应， 直接转化为啮齿动物模型中使用的靶标。第三，我们在休息时使用功能性神经成像， 在情感以及奖励相关的任务，以量化神经回路动态的基础经验， 氯胺酮和摇头丸引起的行为我们将扩展我们的方法来表征个体变异性 在药物诱导的大脑行为经验的档案和锚我们解释这些档案的会计 潜在混杂因素，包括基线受试者间变异性和药物诱导的生化 应力我们使用精确控制的设计来解决我们的目标和大脑如何- 行为机制产生这些药物的主观效果，有助于了解谁寻求使用 他们和为什么。这些发现将促进我们对是什么促使人们使用这些产品的科学理解 药物，并承诺为调查量身定制的干预策略提供基础。手持 有了这些知识，我们的领域最终将能够更好地提出更有效的预防战略， 这些药物的有害使用。

PROJECT SUMMARY (Project 4) MDMA (Ecstasy) and ketamine are drugs of abuse steadily gaining in popularity. Compared to more traditional stimulants, however, less is known about their mode of action, their subjective effects, and how these effects promote continued use. Our objective is to integrate self-report, behavior and neural measures to develop a detailed characterization of the real-time effects of MDMA and ketamine. In doing so we will advance our understanding of how drug altered brain states give rise to acute drug experiences and drug use outcomes. We will first use neuroimaging to map both acute influence of these drugs on human experience, focusing on dissociative, affective, and reward-related responses. Second, we will probe drug-induced effects on behavioral targets that directly translate to targets used in rodent models. Third, we use functional neuroimaging at rest and during affective as well as reward-related tasks to quantify neural circuit dynamics that underlie experiences and behaviors induced by ketamine and MDMA. We will extend our approach to characterizing individual variability in drug-induced brain-behavior-experience profiles and anchor our interpretation of these profiles by accounting for potential confounding factors that include baseline inter-subject variability and drug-induced biochemical stress. We use precisely controlled designs to address our aims and the important question of how brain- behavior mechanisms produce the subjective effects of these drugs, helping to understand who seeks to use them and why. The findings will advance our scientific understanding of what motivates people to use these drugs and promise to provide a foundation for investigating tailored intervention strategies. Armed with this knowledge, our field will ultimately be better positioned to suggest more effective strategies prevention of the harmful use of these drugs.