Network Theory Analysis of Ethanol Self Administering Non-Human Primates

描述(申请人提供)：随着美国医疗保健的经济成本持续上升，与酗酒和依赖相关的问题正成为一个日益严重的问题。因此，解决和治疗酒精滥用和依赖的研究有助于我们对这种疾病的理解。通过了解导致酒精依赖的机制，药物和治疗可以更好地为治疗这种疾病量身定做。长期酗酒与大脑活动减少有关，会影响两种关键的神经递质--GABA(氨基丁酸)和谷氨酸。虽然导致酒精依赖的一些机制和生理变化已经被很好地理解，但不清楚的是这些变化可能发生的时间进程。部分原因是依赖于啮齿动物的研究，由于神经生物学和解剖学的差异，这些研究不容易转化为人类。此外，对人体的研究通常是在临床人群中进行的，这可能不会推广到普通酗酒人群，他们中的许多人没有症状，不寻求治疗。目前在酒精研究中的许多发现都使用了特定地区的模型来研究酒精。然而，大脑是一个由多个相互作用的组件组成的复杂系统，这使得一些发现很难解释。这项拟议的研究将通过利用功能磁共振成像(FMRI)来研究长期自我注射乙醇的非人类灵长类动物的功能变化，从而解决酒精研究中发现的一些关键问题。使用大脑的网络理论来分析我们的数据，我们计划证明fMRI网络可以用来评估酒精依赖带来的大脑变化。在这项研究中，我们将使用我们经过充分验证的动物模型来帮助我们了解长期自我注射乙醇的马鞭猴网络的变化，这可能有助于深入了解导致酒精依赖的人类大脑的变化。 与公共健康相关：随着美国医疗保健的经济成本持续上升，与酗酒和依赖相关的问题正成为一个日益严重的问题。因此，研究酒精滥用和依赖的机制有助于我们理解这种疾病。在这项研究中，我们将研究乙醇诱导后的非人类灵长类动物的大脑网络，以评估长期酒精暴露对它们全脑连接的变化。

DESCRIPTION (provided by applicant): As the economic cost of healthcare continues to rise in the United States, the issues related to alcohol abuse and dependence are becoming an increasing problem. Consequently, research addressing and treating alcohol abuse and dependence is instrumental to our understanding of the disease. By understanding the mechanisms that lead to alcohol dependence, medications and treatments can be better tailored to treating the disease. Chronic alcohol abuse is linked to reductions in brain activity, affecting two key neurotransmitters, GABA (-aminobutyric acid) and glutamate. While some of the mechanisms and physiological changes that lead to alcohol dependence are well understood, what is not clear is the time course in which these changes might occur. The time course is not understood partially because of reliance on rodent studies, which do not easily translate to humans due to differences in neurobiology and anatomy. In addition, studies in humans are typically done in clinical populations, which may not generalize to the general alcoholic population, many of whom are asymptomatic and do not seek treatment. Many current findings in alcohol research employ region- specific models to study alcohol. However, the brain is a complex system with multiple interacting components, which makes some findings difficult to interpret. The proposed study will address some of these critical issues found in alcohol research by utilizing functional magnetic resonance imaging (fMRI) to investigate the functional changes in non-human primates that have chronically self-administered ethanol. Using network theory of the brain to analyze our data, we plan to demonstrate that fMRI networks can be used to assess the changes in the brain brought about by alcohol dependence. During this study, we will use our well-validated animal model to help us understand the changes in the networks of vervet monkeys that have chronically self-administered ethanol, which may offer insight into the changes in the human brain that lead to alcohol dependence. PUBLIC HEALTH RELEVANCE: As the economic cost of healthcare continues to rise in the United States, the issues related to alcohol abuse and dependence are becoming an increasing problem. Consequently, research into the mechanisms underlying alcohol abuse and dependence is instrumental to our understanding of the disease. During this study, we will study the brain networks of non-human primates after ethanol induction to evaluate the changes in their whole-brain connectivity due to chronic alcohol exposure.