LIMBIC MONOAMINE SYSTEMS IN EXCESSIVE ETHANOL SELF-ADMINISTRATION

过量乙醇自我施用中的边缘单胺系统

• 批准号: 6969894
• 负责人: ALLYSON J BENNETT
• 金额: $ 21.24万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-08-20 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6969894
• 关键词: Macaca fascicularis; alcoholism /alcohol abuse; amines; behavior test; cardiovascular function; cognition; disease /disorder proneness /risk; ethanol; limbic system; memory; neuroendocrine system; relapse /recurrence; self medication

Human alcohol research and clinical practice demonstrate without question that individual variation in risk for excessive drinking, in sensitivity to alcohol effects, and in response to treatment strategies are critical to understanding the disorder. Effective prevention strategies for alcoholism rest on successful identification of factors that increase the likelihood for developing heavy patterns of alcohol consumption, while effective treatment strategies rest on elucidating factors that increase vulnerability to deleterious consequences of alcohol exposure and increased danger of relapse. Risk factors for excessive drinking, as well as individual variation in the consequences of alcohol exposure, are key research targets. Nonhuman primates provide an optimal model for this type of translational research. Nonhuman primates exhibit the entrenched, abusive patterns of alcohol drinking that characterize human alcoholism, but they also show variation in drinking patterns. We propose to use this model, along with affective and behavioral profiles drawn from multiple experimental tests, in order to identify candidate predictive factors for excessive alcohol consumption. Using a longitudinal design, as well as between-groups analysis we broadly aim to examine the behavioral and physiological correlates of vulnerability (or resilience) to abusive patterns of ethanol consumption and to determine the effects of alcohol consumption on four crucial targets impulsivity/novelty-seeking/inhibitory control; memory and cognition; cardiac signal dynamics; and menstrual cycle). Finally, we will characterize an acute phase of withdrawal for behavioral signs of withdrawal and cardiac arrhythmias, and associate these changes with individual alcohol intake patterns. Specific Airms are 1) To examine the relationship between central aspects of temperament (impulsivity, novelty-seeking, inhibitory control), memory, cognition and individual risk for excessive alcohol self-administration. 2) To determine the effect of alcohol--both in fixed dose (induction) and ad libitum self-administration (1-year)--on temperament, memory, and cognition. 3) To determine the effect of both fixed-dose and long-term alcohol self-administration on cardiac and neuroendocrine function. 4) To describe the behavioral and physiological sequelae of withdrawal (24-hr) after long-term (12-mo) alcohol self-administration

人类酒精研究和临床实践无疑表明，过度饮酒的风险、对酒精影响的敏感度和治疗策略的个体差异对于理解这种疾病至关重要。有效的酒精中毒预防策略有赖于成功地找出增加大量饮酒的可能性的因素，而有效的治疗策略则有赖于查明增加易受酒精暴露有害后果影响的因素和增加复发危险的因素。过度饮酒的危险因素，以及个人 酒精暴露的后果的差异，是关键的研究目标。非人灵长类动物为这种类型的翻译研究提供了一个最佳模型。非人灵长类动物表现出根深蒂固的、滥用酒精的模式，这是人类酒精中毒的特征，但它们也表现出饮酒模式的变化。我们建议使用这个模型，以及从多个实验测试中提取的情感和行为特征，以确定过度饮酒的候选预测因素。使用纵向设计以及组间分析，我们的主要目标是检验酒精消费滥用模式下的脆弱性(或弹性)与行为和生理上的相关性 确定饮酒对四个关键目标的影响(冲动/寻求新奇/抑制控制；记忆和认知；心脏信号动力学；和月经周期)。最后，我们将描述戒断的急性阶段的戒断行为迹象和心律失常，并将这些变化与个体酒精摄入模式联系起来。具体的航空公司有 1)考察气质(冲动、寻求新奇、抑制性控制)、记忆、认知与个体过度饮酒风险之间的关系。 2)确定酒精对气质、记忆和认知的影响--包括固定剂量酒精(诱导法)和随机给药法(1年)。 3)确定固定剂量和长期酒精给药对心脏和神经内分泌功能的影响。 4)描述长期(12个月)饮酒后戒断(24小时)的行为和生理后遗症