Oxytocin Deficit in Heavy Alcohol Drinkers

项目摘要 酒精使用障碍（AUD）是美国和世界范围内的一个主要公共卫生问题， 一些FDA批准的药物并不是对每个人都有效。最近神经肽催产素， 被提出作为酒精使用障碍的潜在治疗方法，但其背后的神经机制 治疗潜力是难以捉摸的。阐明酒精对中枢催产素水平的慢性影响 神经系统是必不可少的，以帮助了解其治疗机制，并最终确定患者， 会从治疗中得到最大的好处。然而，获得催产素的直接措施， 人类的中枢神经系统是复杂的或不可能的，并且通常脑中催产素的水平是 根据已知的血液浓度推测。然而，中枢和血液水平之间的关系 催产素的水平尚不清楚，需要动物研究来揭示酒精对催产素水平的长期影响， 探讨中枢与血液催产素水平的关系。 非人灵长类动物为人类酒精使用障碍提供了一个非常有益的翻译模型 由于它们与人类的遗传、解剖和生理相似性， 他们自愿饮酒量的个体差异。在这个项目中，我们建议测量 垂体组织、脑脊液和血液样本中的内源性催产素水平， 这些猴子接受了12个月的标准酒精自我给药方案。首先，我们将测试 垂体和CSF中的催产素水平随着酒精摄入量的增加而降低（目的1）。那么我们将 测试垂体和CSF中催产素的水平是否对应于 灵长类动物（目标2）。因此，该项目将提供大量饮酒时催产素水平的重要证据。 个人，并将显着有助于个性化使用潜在的催产素的方法 酒精使用障碍的治疗。

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.