Unraveling Epigenetic Mechanisms Of Opioid Addiction Susceptibility Using Multigenerational Animal Models

项目摘要 吸毒成瘾是一个巨大的公共卫生问题，给我们的经济和社会造成了广泛的负担。 滥用毒品的有害后果远远超出吸毒者的范围，并严重影响其家庭。一 越来越多的证据表明，父亲在1998年前后吸毒的孩子， 怀孕会改变大脑功能和行为异常。我们已经建立了一个高度 翻译范式的父亲阿片类药物服用，使用吗啡自我管理的大鼠研究这一点 现象我们的研究结果表明，长期服用吗啡的父亲（父系）的雄性后代， 更容易产生上瘾的特征，并自我注射吗啡。这几代人 动物模型提供了一个罕见的窗口，让我们了解更容易上瘾的受试者， 这是一个历史上很难识别的群体。在这里，我们可以可靠和系统地生产 动物表现出增加的吸毒行为，这提供了一个独特的机会，深入研究 成瘾易感性的潜在机制这个多方面的项目将结合联合收割机的行为和 分子生物学方法，以确定功能相关的机制，赋予更高的倾向， 发展成瘾。 父母奖和相关研究解决了两个主要问题：（1）哪些生殖系表观遗传 重编程事件对成年后成瘾易感性的发展至关重要？（二） 什么是功能相关的神经表观遗传过程，增加成瘾样的行为，在我们的 多代吸毒的模式这一补充将支持NIDA暑期实习生谁将接受培训 发展研究技能，包括数据收集、数据管理、统计分析和传播 （书面和口头）或结果。

PROJECT SUMMARY Drug addiction is a massive public health concern that inflicts extensive burdens on our economy and society. The harmful consequences of drug abuse extend far beyond the addicts and gravely impact their families. A growing body of evidence suggests that the children of fathers who consumed drugs around the time of conception show altered brain function and behavioral abnormalities. We have established a highly translational paradigm of paternal opioid drug taking, using morphine self-administration in rats to study this phenomenon. Our results demonstrate that the male progeny of fathers (sires) that took morphine chronically are more susceptible to develop addiction-like traits and self-administer morphine. This multigenerational animal model offers a rare window into a pool of subjects that are more vulnerable to develop addiction, a population that has been historically difficult to identify. Here, we can reliably and systematically produce animals that show increased drug taking behavior, which offers a unique opportunity to delve into the mechanisms underlying addiction susceptibility. This multifaceted project will combine behavioral and molecular biological approaches to identify functionally relevant mechanisms that confer a higher propensity to develop addiction. The parent award and related studies address two major questions: (1) which germline epigenetic reprogramming events are critical for shaping development toward addiction vulnerability into adulthood? (2) what are the functionally relevant neuro-epigenetic processes that increase addiction-like behavior in our multigenerational model of drug taking? This supplement will support a NIDA summer intern who will be trained to develop research skills including data collection, data management, statistical analysis and dissemination (written and oral) or results.