Alcohol Tolerance and Behavioral Disinhibition in Humans

项目摘要 酒精耐受性是指随着重复剂量的增加，反应强度减弱。宽容有 长期以来一直被认为是导致酗酒和依赖的一个因素，因为它鼓励使用 增加剂量以恢复药物的初步效果。酒精的急性损害作用也是众所周知的。 涉及行为和注意力调节的神经认知过程。然而，几乎没有研究表明 研究了这种干扰如何可能减少对实际饮酒的自我控制，导致模式 滥用饮酒(例如，酗酒)。此外，尽管对耐受性作为一种表型标记感兴趣， 酒精使用障碍，很少有研究试图确定酒精敏感性和 耐受性可能是酗酒高危人群的特征，例如那些有外在性障碍的人群 (例如，ADHD)。这项建议是基于酒精滥用潜力被确定的工作假设 通过对它的奖励增强作用和抑制作用的敏感性。拟议的研究审查了 耐受性对滥用潜力的贡献，通过酒精对基本机制的影响来衡量 参与控制和规范行为的。研究将调查：1)控制的敏感性 酒精损害效应的机制及其对滥用潜能的贡献；2)耐受性 对控制行为和注意力的机制的损害作用的发展；3) 对酒精滥用潜力的耐受性；4)抑制和注意力缺陷的程度 与ADHD相关的影响酒精敏感性和耐受性的发展；以及5) 联合使用常用兴奋剂对耐受性的发展过程有何影响？ 在ADHD的管理中。

Project Abstract Alcohol tolerance refers to a diminished intensity of response as doses are repeated. Tolerance has long been implicated as a factor contributing to alcohol abuse and dependence by encouraging the use of escalating doses to reinstate initial effects of the drug. Alcohol is also well-known for its acute impairing effects on neurocognitive processes involved in the regulation of behavior and attention. Yet, little research has examined how such disturbances might reduce self-control over actual alcohol use, leading to patterns of abusive drinking (e.g., binge drinking). Moreover, despite interest in tolerance as a phenotypic marker for alcohol use disorders, little research has sought to determine how differences in alcohol sensitivity and tolerance might characterize populations at-risk for alcohol abuse, such as those with externalizing disorders (e.g., ADHD). The proposal is based on the working hypothesis that abuse potential of alcohol is determined by sensitivity to its reward-enhancing effects and to its disinhibiting effects. The proposed studies examine the contribution of tolerance to abuse potential as measured by changes in alcohol effects on basic mechanisms involved in the control and regulation of behavior. Studies will investigate: 1) the sensitivity of control mechanisms to the impairing effects of alcohol and their contribution to abuse potential; 2) tolerance development to the impairing effects on mechanisms that control behavior and attention; 3) the contribution of such tolerance to the abuse potential of alcohol; 4) the degree to which the inhibitory and attentional deficits associated with ADHD influence alcohol sensitivity and the development of tolerance; and 5) the degree to which the developmental course of tolerance is affected by concomitant use of stimulant drugs commonly used in the management of ADHD.