Oxytocin Deficit in Heavy Alcohol Drinkers

项目摘要 酒精使用障碍(AUD)在美国和世界范围内是一个主要的公共卫生问题，极其有限 FDA批准的并非对所有人都有效的药物数量。最近一种神经肽，催产素， 被认为是一种潜在的酒精使用障碍的治疗方法，但其背后的神经机制 治疗的潜力是难以捉摸的。慢性酒精对中枢催产素水平影响的研究 神经系统对帮助了解其治疗机制并最终识别出 将从治疗中获得最大的好处。然而，获得直接测量催产素的方法 人类的中枢神经系统是复杂的或不可能的，大脑中催产素的水平经常是 根据已知的血液浓度推测。尽管如此，中枢和血液水平之间的关系 催产素的作用尚不清楚，需要进行动物研究来揭示酒精对脑内催产素水平的慢性影响。 并探讨中枢催产素水平与血液中催产素水平的关系。 非人灵长类动物为人类酒精使用障碍提供了一个特别有益的翻译模型 由于它们在基因、解剖学和生理上与人类相似，而且它们表现出广泛的 他们自愿饮酒量的个体差异。在这个项目中，我们建议测量 脑垂体组织、脑脊液和血液中内源性催产素的水平 这些猴子接受了12个月的标准酒精自我给药方案。首先，我们将测试是否 随着酒精摄入量的增加，脑下垂体和脑脊液中的催产素水平降低(目标1)。那我们就会 脑下垂体和脑脊液中催产素水平与血中催产素浓度 灵长类(目标2)。因此，该项目将提供大量饮酒后催产素水平的重要证据。 并将大大有助于实现潜在催产素的个性化使用 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.