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

人类药物改变状态的脑回路、行为和经验特征

基本信息

批准号：
10494008
负责人：
Leanne Williams
金额：
$ 32.12万
依托单位：
STANFORD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-09-01 至 2028-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10494008
关键词：
Accounting Acute Address Affective Air Award Back Behavior Behavioral Behavioral Mechanisms Biochemical Biological Markers Blinking Brain Cognitive Complex Corpus striatum structure Cues Data Dissociation Dose Drug usage Emotional Empathy Eye Foundations Funding Goals Hour Human Hydrocortisone Individual Intervention Intoxication Ketamine Knowledge Maps Measures Memory Modeling Nature Nociception Outcome Patient Self-Report Persons Pharmaceutical Preparations Phase Placebo Control Placebos Positioning Attribute Prevention strategy Procedures Reaction Time Resolution Rest Rewards Rodent Model Sampling Sensory Stimulant Stimulus Stress Testing Thalamic structure Time Translating Translations Work animal data behavior observation behavior test brain behavior cognitive function design drug action drug of abuse ecstasy executive function experience human data human subject individual variation innovation interest mouse model negative affect neural neural circuit neurobiological mechanism neuroimaging perceived stress response reward circuitry social

项目摘要

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.

项目概要（项目 4） MDMA（摇头丸）和氯胺酮是逐渐流行的滥用药物。相比更多然而，人们对传统兴奋剂的作用方式、主观效果以及如何作用知之甚少。这些效果促进了继续使用。我们的目标是整合自我报告、行为和神经测量详细描述 MDMA 和氯胺酮的实时影响。这样做我们将前进我们对药物如何改变大脑状态导致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影像学来绘制这些药物对人类体验的急性影响，重点关注解离、情感和奖励相关的反应。其次，我们将探讨药物对行为的影响直接转化为啮齿动物模型中使用的目标的目标。第三，我们在休息和休息时使用功能性神经影像学在情感以及与奖励相关的任务中，量化作为体验和奖励基础的神经回路动态氯胺酮和 MDMA 诱导的行为。我们将扩展我们的方法来表征个体差异药物引起的大脑行为体验概况，并通过会计来锚定我们对这些概况的解释潜在的混杂因素，包括基线受试者间变异和药物引起的生化压力。我们使用精确控制的设计来解决我们的目标以及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以及为什么。这些发现将促进我们对人们使用这些技术的动机的科学理解药物并有望为研究定制干预策略提供基础。武装有有了这些知识，我们的领域最终将能够更好地提出更有效的策略来预防这些药物的有害使用。