Oxytocin Deficit in Heavy Alcohol Drinkers

酗酒者的催产素缺乏

• 批准号: 10229474
• 负责人: KATHLEEN A GRANT
• 金额: $ 8.75万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-05 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10229474
• 关键词: Acute; Address; Alcohol abuse; Alcohol consumption; Alcoholic beverage heavy drinker; Alcohols; Anatomy; Animals; Behavior; Blood; Blood Circulation; Blood specimen; Brain; Categories; Cerebrospinal Fluid; Chronic; Clinical Research; Complex; Exhibits; FDA approved; Genetic; Grant; Heavy Drinking; Human; Hypothalamic structure; Individual; Individual Differences; Intake; Investigation; Laboratories; Light; Link; Liquid Chromatography; Measures; Methods; Monkeys; Neuraxis; Neurons; Neuropeptides; Oxytocin; Patients; Pharmaceutical Preparations; Physiological; Pituitary Gland; Plasma; Primates; Procedures; Protocols documentation; Public Health; Regulation; Role; Sampling; Self Administration; Social Behavior; Testing; Therapeutic; Tissues; Water; aged; alcohol abuse therapy; alcohol availability; alcohol effect; alcohol use disorder; base; brain tissue; chronic alcohol ingestion; drinking; experimental study; magnocellular; meetings; nonhuman primate; parvocellular; prospective; prospective test; tandem mass spectrometry; translational model; Acute; Address; Alcohol abuse; Alcohol consumption; Alcoholic beverage heavy drinker; Alcohols; Anatomy; Animals; Behavior; Blood; Blood Circulation; Blood specimen; Brain; Categories; Cerebrospinal Fluid; Chronic; Clinical Research; Complex; Exhibits; FDA approved; Genetic; Grant; Heavy Drinking; Human; Hypothalamic structure; Individual; Individual Differences; Intake; Investigation; Laboratories; Light; Link; Liquid Chromatography; Measures; Methods; Monkeys; Neuraxis; Neurons; Neuropeptides; Oxytocin; Patients; Pharmaceutical Preparations; Physiological; Pituitary Gland; Plasma; Primates; Procedures; Protocols documentation; Public Health; Regulation; Role; Sampling; Self Administration; Social Behavior; Testing; Therapeutic; Tissues; Water; aged; alcohol abuse therapy; alcohol availability; alcohol effect; alcohol use disorder; base; brain tissue; chronic alcohol ingestion; drinking; experimental study; magnocellular; meetings; nonhuman primate; parvocellular; prospective; prospective test; tandem mass spectrometry; translational model

Project Summary Alcohol use disorder (AUD) is a major public health concern in the US and worldwide with extremely limited number of FDA approved medications that are not effective in everyone. Recently the neuropeptide, oxytocin, was proposed as a potential treatment for alcohol use disorder, but the neuronal mechanism underlying its therapeutic potential is elusive. Elucidating chronic effects of alcohol on levels of oxytocin in the central nervous system is essential to help understand its therapeutic mechanism and eventually identify patients that would receive the greatest benefit from the treatment. However, acquiring direct measures of oxytocin in the central nervous system of humans is complex or impossible, and frequently brain levels of oxytocin are assumed based on known blood concentrations. Nevertheless, a relation between the central and blood levels of oxytocin is unclear and animal studies are needed to reveal chronic effects of alcohol on levels of oxytocin in the central nervous system and to explore the relation between the central and blood levels of oxytocin. Nonhuman primates provide an exceptionally beneficial translational model for human alcohol use disorder due to their genetic, anatomical, and physiological similarities to humans, and because they exhibit wide individual differences in the amount of alcohol they voluntarily drink. In this project we propose to measure levels of endogenous oxytocin in the pituitary tissue, cerebral spinal fluid and blood samples collected from monkeys that underwent a standard alcohol self-administration protocol for 12 months. First, we will test if levels of oxytocin in the pituitary and CSF decrease with an increase in alcohol intake (Aim 1). Then we will test whether levels of oxytocin in the pituitary and CSF correspond to blood concentration of oxytocin in primates (Aim 2). Thus, this project will provide important evidence on oxytocin levels across heavy drinking individuals and would significantly aid in the approach toward personalized use of the potential oxytocin therapy for alcohol use disorder.

项目摘要 酒精使用障碍（AUD）是美国的主要公共卫生问题，在全球范围内极为有限 FDA批准的药物数量无效。最近神经肽催产素， 被提出是对酒精使用障碍的潜在治疗方法，但是神经元机制的基础 治疗潜力难以捉摸。阐明酒精对中央催产素水平的慢性影响 神经系统对于帮助了解其治疗机制至关重要，并最终确定患者 将从治疗中获得最大的好处。但是，获取直接测量的催产素 人类的中枢神经系统是复杂的或不可能的，大脑的催产素水平经常是 假定基于已知的血液浓度。然而，中央和血液水平之间的关系 催产素不清楚，需要动物研究来揭示酒精对催产素水平的慢性影响 中枢神经系统并探索催产素的中枢和血液水平之间的关系。 非人类灵长类动物为人类酒精使用障碍提供了异常有益的翻译模型 由于它们与人类的遗传，解剖和生理相似性，并且由于它们表现广泛 他们自愿饮用的酒精量的个体差异。在这个项目中，我们建议衡量 垂体组织中的内源性催产素水平，脑脊髓液和从中收集的血液样本 猴子经过了标准的酒精自我管理方案12个月。首先，我们将测试是否 垂体中的催产素水平随着酒精摄入量的增加而降低（AIM 1）。然后我们会 测试垂体和CSF中的催产素水平是否对应于催产素的血液浓度 灵长类动物（目标2）。因此，该项目将提供有关大量饮酒的催产素水平的重要证据 个人，并且将大大有助于实现潜在催产素的个性化使用方法 饮酒障碍治疗。