Alcohol Tolerance and Behavioral Disinhibition in Humans

项目摘要 酒精耐受性是指随着剂量的重复，反应强度降低。容忍 长期以来一直被认为是导致酒精滥用和依赖的一个因素，因为它鼓励使用 逐步增加剂量以恢复药物的初始效果。酒精也是众所周知的急性损害作用 研究涉及行为和注意力调节的神经认知过程。然而，很少有研究 研究了这种干扰如何可能会降低对实际饮酒的自我控制，导致 酗酒（例如，豪饮）。此外，尽管对耐受性作为表型标记感兴趣， 酒精使用障碍，很少有研究试图确定酒精敏感性和 耐受性可能是酒精滥用风险人群的特征，例如那些患有外化障碍的人群 (e.g., ADHD）。该提案是基于工作假设，即酒精的滥用潜力是确定的 通过对奖励增强效应和抑制效应的敏感性。拟议的研究审查了 通过改变酒精对基本机制的影响来衡量耐受性对滥用潜力的贡献 参与行为的控制和调节。研究将调查：1）控制的敏感性 酒精损害作用的机制及其对滥用潜力的贡献; 2）耐受性 发展对控制行为和注意力的机制的损害作用; 3） 这种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;和5）程度， 其耐受性的发展过程受到常用的兴奋剂药物的伴随使用的影响 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.