Chronic Alcohol and Brain Stress Circuit Response

慢性酒精和脑应激回路反应

• 批准号: 7760032
• 负责人: Rajita Sinha
• 金额: $ 58.66万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-01-20 至 2013-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7760032
• 关键词: Acute; Address; Affect; Alcohol abuse; Alcohol consumption; Alcohol dependence; Alcohol withdrawal syndrome; Alcoholic beverage heavy drinker; Alcoholism; Alcohols; Arousal; Behavioral; Biochemical; Biochemical Markers; Blood Pressure; Brain; Cessation of life; Chronic; Cognitive; Complement component C1s; Corticotropin; Cues; Development; Disease; Distress; Emotions; Endocannabinoids; Exposure to; Family history of; Foxes; Funding; Gender; Guided imagery; Heart Rate; Heavy Drinking; Human; Hydrocortisone; Hypotension; Imagery; Individual; Individual Differences; Inpatients; Intervention; Laboratories; Length of Stay; Literature; Measures; Mental disorders; Motivation; Nicotine; Pathway interactions; Pattern; Physiological; Play; Predisposition; Prevention; Procedures; Progress Reports; Race; Relapse; Rewards; Risk; Role; Sampling; Series; Severities; Stress; Symptoms; Taste Perception; Testing; addiction; alcohol craving; alcohol cue; alcohol relapse; alcohol response; alcohol seeking behavior; anandamide; behavior measurement; binge drinker; binge drinking; biological adaptation to stress; craving; design; drinking; neuroadaptation; problem drinker; response; stressor

DESCRIPTION (provided by applicant): Chronic Alcohol and Brain Stress Circuit Response Alcoholism is a chronic relapsing illness in which alcohol-related neuroadaptations in brain stress and reward pathways are known to promote persistent craving or compulsive alcohol seeking, a hallmark symptom in both the development of alcoholism and in alcohol relapse susceptibility. In the first funding period of this project, we found that chronic alcohol abuse is associated with a series of stress-related alterations that accompany the compulsive alcohol seeking state, and these changes contribute to high relapse susceptibility in alcoholics completing inpatient treatment. Furthermore, preliminary results comparing moderate (MD), moderate bingeing (MB) and heavy (HD) non-dependent drinkers studied in the current period suggested a progressive increase in sensitivity to stress-induced and cue-induced alcohol craving and associated physiological and biochemical alterations associated with heavy drinking and/or binge drinking. These findings suggest that alcohol-related alterations in stress responses and stress and cue-induced craving may contribute to the development of compulsive alcohol seeking. Therefore, in this competing renewal application, we extend and expand the findings from the current period to examine the role of stress in the development of compulsive alcohol seeking and in increased stress and cue-related alcohol consumption in non-dependent heavy and binge drinkers. A 5-year project with a cross-sectional design is proposed that will study demographically-matched samples of 50 MD, 50 MB and 50 HD drinkers, to address the following specific aims: (1) To examine whether exposure to stress and to alcohol cues increases alcohol craving, negative emotions, behavioral distress responses and alters physiological and biochemical responses differentially across the three drinking groups. (2) To examine whether exposure to stress and to alcohol cues vs. neutral cues increases alcohol consumption in the alcohol taste test, and if amount consumed vary as a function of drinking group. (3) To examine whether subjective, physiological and biochemical markers of distress and compulsive seeking is predictive of amounts of alcohol consumed in each condition. (4) To examine the influence of demographic and individual differences variables, such as gender, race, family history of alcoholism (FH), co-morbid use of nicotine and poor cognitive/impulse control in stress and cue-related responses and level of alcohol consumption. Addressing these questions will increase an understanding of the mechanisms by which alcohol consumption and stress responses interact to influence development of compulsive alcohol seeking and vulnerability to loss of control drinking, and the results will have significant implications for the development of new prevention and treatment interventions for alcoholism. Alcoholism is among the top three causes of preventable death and disease in the US (Mokdad et al., 2004; Room et al., 2005). Stress plays an important role in the development of alcoholism and in high vulnerability to alcohol relapse. The proposed study will provide a greater understanding of the mechanism by which stress and alcohol consumption interacts to influence development of compulsive alcohol seeking and vulnerability to stress-induced drinking, and the results will have significant implications for the development of new prevention and treatment interventions for alcoholism.

描述（由申请人提供）：慢性酒精和大脑压力回应酒精中毒是一种慢性复发性疾病，其中与酒精相关的脑压力和奖励途径中与酒精相关的神经适应性促进持续的渴望或强迫性酒精，这是酒精中毒和酒精中毒的发展和酒精复发易感性的症状。在该项目的第一个资金期间，我们发现慢性酒精滥用与一系列与压力相关的变化有关，这些变化伴随着强迫性酒精寻求状态，这些变化有助于在酒精中毒中高复发敏感性，以完成住院治疗。此外，在当前期间研究的中度（MD），中度暴饮暴食（MB）和重量（HD）非依赖性饮酒者的初步结果表明，对压力诱导和提示诱导的酒精渴望和相关的生理和生理和生物化学变化的敏感性逐渐增加，与饮酒和饮酒相关。这些发现表明，与酒精相关的压力反应和压力和提示引起的渴望的改变可能有助于寻求强迫性酒精。因此，在这种相互竞争的续订应用中，我们从当前时期扩展并扩展了发现的结果，以研究压力在寻求强迫性酒精以及增加压力和提示相关的饮酒量中的作用中，在非依赖性繁重和暴饮暴食中。提出了一个5年的横截面设计项目，该项目将研究50 MD，50 MB和50 HD饮酒者的人口统计学匹配样本，以解决以下具体目的：（1）检查压力和酒精提示是否会增加酒精的渴望，负面情绪，行为困扰，行为困扰反应，并改变了三分之二的饮酒组。 （2）检查暴露于压力和酒精提示与中性线索是否会增加酒精味道测试中的酒精消耗，并且是否会随着饮酒组的函数而摄入的数量有所不同。 （3）检查遇险和强迫性寻求的主观，生理和生理和生化标记是否可以预测每种情况下消耗的酒精量。 （4）检查人口统计和个体差异变量的影响，例如性别，种族，酒精中毒家族史（FH），在压力和提示相关的反应和饮酒水平中的尼古丁和较差的认知/脉冲控制合并使用。解决这些问题将增加对酒精消耗和压力反应相互作用的机制的理解，以影响强迫性酒精寻求和损失控制饮酒的脆弱性，并且结果将对酗酒的新预防和治疗干预措施产生重大影响。酒精中毒是美国可预防死亡和疾病的三大原因之一（Mokdad等，2004； Room等，2005）。压力在酒精中毒的发展和高度易受酒精复发的能力中起着重要作用。拟议的研究将对压力和酒精消耗相互作用以影响强迫性酒精寻求和易于压力引起的饮酒的发展的机制有更深入的了解，结果将对酗酒的新预防和治疗干预措施产生重大影响。