Alcohol Tolerance and Behavioral Disinhibition in Humans

人类的酒精耐受性和行为抑制

基本信息

批准号：
7934649
负责人：
Mark T Fillmore
金额：
$ 27.72万
依托单位：
UNIVERSITY OF KENTUCKY
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-20 至 2014-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7934649
关键词：
Accounting Acute Acute Alcoholic Hepatitis Adderall Address Adult Affect Alcohol abuse Alcohol consumption Alcohol dependence Alcohols Attention Attention deficit hyperactivity disorder Attentional deficit Behavior Behavior Control Behavioral Behavioral Model Biochemical Characteristics Comb animal structure Cues Dependence Development Disease Disinhibition Dose Drug usage Euphoria Health Human Impairment Informal Social Control Knowledge Laboratories Laboratory Animals Learning Liver Cirrhosis Measures Methods Methylphenidate Modeling Naltrexone Neurocognitive Pattern Pharmaceutical Preparations Pharmacotherapy Play Populations at Risk Predisposition Procedures Process Regulation Reporting Research Rewards Risk Risk Factors Role Self Administration Self-control as a personality trait Series Signal Transduction Study Section Techniques Testing Training Treatment Efficacy Work acamprosate alcohol and other drug alcohol effect alcohol exposure alcohol poisoning alcohol sensitivity alcohol use disorder base binge drinking disinhibitory psychopathology drinking drinking behavior early onset interest programs public health relevance response

项目摘要

DESCRIPTION (provided by applicant): 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. PUBLIC HEALTH RELEVANCE: Excessive alcohol use contributes to many adverse health consequences (e.g., alcohol poisoning, acute alcoholic hepatitis and liver cirrhosis). 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. Yet, little research has examined how tolerance might increase the risk for alcohol abuse. The proposed studies examine the contribution of tolerance to abuse potential as measured by changes in the ability of the drug to alter basic mechanisms involved in the control and regulation of behavior. The findings of this research will provide an understanding of how drinkers' susceptibility to alcohol's acute behavioral-impairing effects can pose an early-onset risk factor for later alcohol dependence by promoting a continued pattern of abusive binge drinking. The research strategies also will provide methods for testing the role of neurocognitive mechanisms in the treatment efficacy of existing pharmacotherapies, such as naltrexone and acamprosate, as well as some investigational medications that might operate via neurocognitive control mechanisms.

描述（由申请人提供）：酒精耐受性是指重复剂量时的反应强度降低。长期以来，长期以来，通过鼓励使用不断升级的剂量来恢复药物的初始作用，将耐受性视为导致酗酒和依赖性的一个因素。酒精也因其对行为和注意力调节的神经认知过程的急性损害影响而闻名。然而，很少的研究研究了这种障碍如何减少实际使用酒精的自我控制，从而导致滥用饮酒的模式（例如，暴饮暴食）。此外，尽管对耐受性作为对酒精使用障碍的表型标记的兴趣，但很少的研究试图确定酒精敏感性和耐受性的差异如何表征在饮酒中滥用酒精（例如患有外在性疾病的人）（例如，ADHD）。该提议基于这样的假设，即酒精的滥用潜力取决于对其奖励增强作用及其消除抑制作用的敏感性。拟议的研究研究了耐受性对滥用潜力的贡献，这是通过酒精对控制和调节的基本机制的影响衡量的。研究将研究：1）控制机制对酒精损害及其对滥用潜力的贡献的敏感性； 2）对控制行为和注意力的机制产生损害的影响； 3）这种宽容对酒精滥用潜力的贡献； 4）与多动症相关的抑制性和注意力缺陷影响酒精敏感性和耐受性的发展程度； 5）耐受性的发育过程受到多动症管理中常用的刺激药物的影响。公共卫生相关性：过度使用饮酒会导致许多不良健康后果（例如，酒精中毒，急性酒精性肝炎和肝肝硬化）。长期以来，长期以来，通过鼓励使用不断升级的剂量来恢复药物的初始作用，将耐受性视为导致酗酒和依赖性的一个因素。然而，很少的研究研究了容忍度如何增加酗酒的风险。拟议的研究研究了耐受性对滥用潜力的贡献，这是通过药物改变行为控制和调节所涉及的基本机制的能力的变化来衡量的。这项研究的发现将对饮酒者对酒精急性行为障碍效果的敏感性如何通过促进持续的虐待暴饮暴食方式来构成后来的酒精依赖的危险因素。该研究策略还将提供测试神经认知机制在现有药物疗法（例如纳曲酮和丙霉菌酯等现有药物疗法的治疗疗效）中的作用的方法，以及某些可能通过神经认知控制机制进行的研究药物。