Dopamine: Alcohol Risk and Sensitivity

多巴胺：酒精风险和敏感性

• 批准号: 6621911
• 负责人: MARY E MCCAUL
• 金额: $ 43.48万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-07-01 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6621911
• 关键词: alcoholic beverage consumption; alcoholism /alcohol abuse; anxiety; bioimaging /biomedical imaging; clinical research; disease /disorder proneness /risk; dopamine receptor; dopamine transporter; family genetics; human subject; neurobiology; neuroimaging; positron emission tomography; psychomotor function; self medication; stress; substance abuse related behavior; young adult human (21-34)

DESCRIPTION (provided by applicant): Multiple neurotransmitter systems are involved in alcohol reinforcement. These systems are altered by environmental and genetic determinants of risk for alcohol use disorders. Recently, there has been considerable attention to the role of mesolimbic dopamine in alcohol and drug reward. For example, it has been demonstrated that D2 dopamine receptor density is negatively related to stimulant liking, such that individuals with low D2R density report more pleasant effects following stimulant administration than individuals with high D2R density. The proposed research will examine relationships between two key PET-derived measures of the dopamine system (D2 receptor density and dopamine transporter density) and alcohol sensitivity and liking. Additionally, the research will characterize the impact of several well-established predictors of alcoholism risk on these associations. Specific alcoholism risk factors will include family history of alcoholism, high trait anxiety and high excitement seeking. Subjects (N=100) will be social drinkers who do not meet diagnostic criteria for alcohol abuse or dependence but who differ on risk factors known to influence alcoholism development. All subjects will undergo a 13-day inpatient protocol that includes PET imaging of D2R and DAT density, and laboratory measurements of alcohol sensitivity and liking. Alcohol-related measures will include subjective, physiological and psychomotor responses to alcohol ingestion. This project represents an important extension of our earlier and current research on alcoholism. Knowledge gained from both this independent R01 proposal and through interaction with the other IRPG proposals will provide critical new scientific and clinical knowledge on involvement of the dopamine neurotransmitter system in alcohol reward, particularly in persons at differential risk for alcoholism.

描述（由申请人提供）：多种神经递质系统 参与酒精强化。这些系统会因环境而改变 以及酒精使用障碍风险的遗传决定因素。近来，有 人们对中脑边缘多巴胺在酒精和酒精中的作用给予了相当多的关注 药物奖励。例如，已证明 D2 多巴胺受体 密度与刺激物的喜好呈负相关，因此具有 低 D2R 密度报告服用兴奋剂后效果更令人愉悦 高于 D2R 密度高的个体。拟议的研究将研究多巴胺系统的两个关键 PET 衍生指标（D2 受体密度和多巴胺转运蛋白密度）与酒精敏感性和喜好之间的关系。此外，该研究还将描述几个公认的酗酒风险预测因素对这些因素的影响。 协会。具体的酗酒风险因素包括家族史 酗酒、高特质焦虑和高兴奋寻求。受试者 (N=100) 将是不符合酒精滥用诊断标准的社交饮酒者 或依赖，但对已知影响酗酒的危险因素有不同看法 发展。所有受试者都将接受为期 13 天的住院治疗方案 包括 D2R 和 DAT 密度的 PET 成像，以及实验室测量 酒精敏感性和喜好。与酒精相关的措施将包括 对饮酒的主观、生理和精神运动反应。这 该项目代表了我们早期和当前研究的重要延伸 关于酗酒。从这个独立的 R01 提案中获得的知识和 通过与其他 IRPG 提案的互动，将提供关键的新内容 关于多巴胺参与的科学和临床知识 酒精奖励中的神经递质系统，特别是在酒精奖励中的人 酗酒的不同风险。