Unraveling epigenetic mechanisms of opioid addiction susceptibility using multigenerational animal models

使用多代动物模型揭示阿片类药物成瘾易感性的表观遗传机制

• 批准号: 10161360
• 负责人: Mathieu Wimmer
• 金额: $ 6.09万
• 依托单位: TEMPLE UNIV OF THE COMMONWEALTH
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-07-15 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10161360
• 关键词: Adolescence; Adult; Affect; Animal Model; Behavior; Behavioral; Biological; Biological Markers; Brain; Child; Conceptions; Consumption; Drug Addiction; Drug abuse; Environmental Risk Factor; Epigenetic Process; Family; Fathers; Gene Expression; Generations; Individual; Lead; Life; Mental disorders; Molecular; Morphine; Neurobiology; Opiate Addiction; Opioid; Pharmaceutical Preparations; Predisposition; Puberty; Public Health; Research; Shapes; Signal Pathway; Societies; Time; addiction; offspring; opioid exposure; trait

Project Summary/Abstract 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. Using a highly translational paradigm of paternal opioid drug taking, this projects aims to identify biomarkers and mechanisms predictive of addiction susceptibility. The focus of the proposed studies will be changes in gene expression and behavior produced by paternal opioid exposure that emerge during adolescence in first generation progeny and are predictive of higher addiction-like traits in adulthood. This multifaceted project will combine behavioral and molecular biological approaches to identify functionally relevant mechanisms during puberty that confer a higher propensity to develop addiction later in life. Overall, this research will establish a strategy to delineate functional mechanisms associated with addiction susceptibility and develop a platform to study how environmental insults can shape and affect the likelihood of individuals to develop psychiatric diseases.

项目摘要/摘要 吸毒成瘾是一个巨大的公共卫生问题，给我们带来了巨大的负担 经济与社会。药物滥用的有害后果远远超出了吸毒者 并严重影响他们的家人。越来越多的证据表明 在受孕期间消费毒品的父亲表明大脑功能改变了 行为异常。使用高度翻译的父亲阿片类药物服用范式 该项目旨在确定可预测成瘾易感性的生物标志物和机制。 拟议研究的重点将是基因表达和产生的行为的变化 在第一代后代的青春期中出现的父亲阿片类药物暴露 预测成年中较高的成瘾性特征。这个多方面的项目将结合起来 行为和分子生物学方法，以识别功能相关的机制 在青春期期间，它赋予了更高的倾向，以便在以后的生活中发展成瘾。总体而言，这 研究将制定一种策略来描述与成瘾相关的功能机制 敏感性并开发一个平台来研究环境侮辱如何塑造和影响 个体发展精神病的可能性。