FMRI OF BIAPHASIC ALCOHOL EFFECTS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 理论和经验证据已经将酒精的更大的双相效应与酒精使用障碍的易感性增加联系起来。就饮酒而言，双相效应指的是刺激和奖励的主要效应(饮酒者在开始饮酒后不久感觉更健谈和不受约束)，但紧随其后的是更镇静、更有害和更令人厌恶的效应(例如，说话含糊，运动协调受限)。双相酒精效应研究的功能磁共振成像将使用强大的大脑成像和分子遗传学技术来评估这种关系，以及调节酒精反应的神经遗传学机制。这项研究将进一步加深我们对酒精的大脑反应及其与导致易感性的基因变异的关系的理解。使用动脉自旋标记来测量局部脑血流量和局部脑酒精水平的功能磁共振成像(FMRI)实验将测试这一模型的各个方面。具体地说，这项研究的目标是：(1)测试纽林开发的一个模型，该模型涉及可能调节对酒精的双相反应的大脑机制。将使用功能性磁共振成像(FMRI)技术[动脉自旋标记(ASL)]来测量调节酒精双相效应的脑机制；(2)确定酒精的静脉血和脑内药代动力学。这将使我们能够扩大我们对静脉血酒精浓度、局部和暂时性脑酒精水平之间的关系的理解；(3)双相局部脑血流和脑酒精水平与成瘾易感性基因之间的关系。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Theory and empirical evidence have linked greater biphasic effects of alcohol to heightened vulnerability to alcohol use disorders. Biphasic effects, in terms of alcohol use, refer to the primary effects that are stimulatory and rewarding (the drinker feels more talkative and uninhibited soon after beginning to drink) but are followed by effects that are more sedating, impairing and aversive (e.g., slurred speech, limited motor coordination). The fMRI of Biphasic Alcohol Effects Study will evaluate this relationship, as well as neurogenetic mechanisms that mediate alcohol response, using powerful brain imaging and molecular-genetic techniques. This research wilsl further our understanding of brain responses to alcohol and their relationship to genetic variants that confer vulnerability. A functional magnetic resonance imaging (fMRI) experiment using arterial spin labeling to measure regional cerebral blood flow and regional brain ethanol levels will test aspects of this model. Specifically, the goals of the study are to: (1) Test a model developed by Newlin concerning brain mechanisms that may mediate the biphasic response to alcohol. Brain mechanisms that mediate the biphasic effects of alcohol will be measured using functional magnetic resonance imaging (fMRI) techniques [arterial spin labeling (ASL)] that allow assessment of regional cerebral blood flow; (2) Determine venous blood and brain pharmacokinetics of alcohol. This will allow us to expand our understanding of the relations among venous blood alcohol concentrations, regional and temporal brain ethanol levels; (3) Relate biphasic regional cerebral blood flow and brain alcohol levels to addiction vulnerability genotypes.