fMRI of the mesolimbic dopamine system in risky drinkers

描述（由申请人提供）：主要研究者的长期目标是使用功能成像来研究导致酒精中毒和治疗复发的边缘系统脆弱性。这些知识对于理解疾病机制和开发药物治疗至关重要。本应用程序的目的是使用功能磁共振成像和酒精相关的嗅觉线索来研究具有不同酒精中毒风险的个体的腹侧被盖区、伏隔核、边缘味觉和眶额皮质。目的1：确定家族史和近期饮酒对中脑边缘多巴胺和味觉区域嗅觉线索诱导反应的影响。我们将使用功能磁共振成像来研究味觉和中脑边缘多巴胺区对酒精气味线索的反应，这些人是非依赖性的、健康的、社交饮酒者，他们因酗酒家族史和最近饮酒而异。目的2：研究低剂量酒精对中脑边缘多巴胺、味觉和眼窝区域线索诱导反应的影响。我们将研究在稳态静脉酒精输注过程中，这些大脑边缘区域嗅觉线索引发信号的组间差异。目的3：研究线索诱导的信号在中脑边缘多巴胺和味觉区域作为线索诱导的渴望的功能。我们将研究暴露于酒精线索后的饮酒欲望和唾液分泌的变化，并将这些变化与fMRI观察到的信号变化联系起来。这项研究的意义在于，它直接将实验动物研究的发现扩展到关键的感兴趣人群——有酗酒风险的人类受试者。这项工作将促进我们对大脑关键区域的功能如何与酒精中毒的两个主要风险因素中的一个或两个相关的理解。

DESCRIPTION (provided by applicant): The principal investigator's long term goal is to use functional imaging to study limbic system vulnerabilities that lead to alcoholism and treatment relapse. This knowledge is essential for understanding disease mechanisms and developing drug treatments. The objective of this application is to use fMRI and alcohol-related olfactory cues to study the ventral tegmental area, nucleus accumbens, limbic gustatory and orbitofrontal cortex in individuals at differential risk for alcoholism. Aim 1: Determine the effects of family history and recent drinking on olfactory cue-induced responses in mesolimbic dopamine and gustatory areas. We will use fMRI to study gustatory and mesolimbic dopamine area responses to alcoholic odor cues in non-dependent, healthy, social drinkers who vary by family history of alcoholism and recent drinking. Aim 2: Study the effects of low-dose alcohol on cue-induced responses in mesolimbic dopamine, gustatory, and orbital areas. We will study group differences in olfactory cue-elicited signals in these limbic brain areas during steady-state, intravenous alcohol infusion. Aim 3: Examine cue-induced signals in mesolimbic dopamine and gustatory areas as a function of cue-induced craving. We will study changes in desire to drink and salivation following exposure to alcohol cues, and relate those changes to observed signal changes in fMRI. The significance of this research is that it directly extends findings from experimental animal research to the key population of interest- human subjects at risk for developing alcoholism. The work will advance our understanding of how brain function in key regions is associated with one or both of two main risk factors for alcoholism.