Network Theory Analysis of Ethanol Self Administering Non-Human Primates

描述（由申请人提供）：随着美国医疗保健的经济成本持续上升，与酒精滥用和依赖有关的问题正在成为一个日益严重的问题。因此，研究解决和治疗酒精滥用和依赖有助于我们了解这种疾病。通过了解导致酒精依赖的机制，药物和治疗可以更好地治疗这种疾病。慢性酒精滥用与大脑活动减少有关，影响两种关键的神经递质，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，但这些变化可能发生的时间过程尚不清楚。由于依赖于啮齿类动物的研究，这一时间过程不被理解，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，对人类的研究通常是在临床人群中进行的，可能无法推广到一般的酗酒人群，其中许多人没有症状，也没有寻求治疗。目前酒精研究的许多发现都采用特定区域的模型来研究酒精。然而，大脑是一个由多个相互作用的组成部分组成的复杂系统，这使得一些发现难以解释。该研究将利用功能性磁共振成像（fMRI）来研究长期自我使用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。利用大脑的网络理论来分析我们的数据，我们计划证明功能磁共振成像网络可以用来评估酒精依赖给大脑带来的变化。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使用乙醇的黑尾猴网络的变化，这可能为了解导致酒精依赖的人类大脑的变化提供洞见。

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.