LIMBIC MONOAMINE SYSTEMS IN EXCESSIVE ETHANOL SELF-ADMINISTRATION

人类酒精研究和临床实践毫无疑问地表明，个体过度饮酒风险的差异，对酒精影响的敏感性以及对治疗策略的反应对于理解这种疾病至关重要。酒精中毒的有效预防战略取决于成功地确定增加发展大量饮酒模式的可能性的因素，而有效的治疗战略则取决于阐明增加易受酒精暴露有害后果影响和增加复发危险的因素。过量饮酒的风险因素，以及个人 酒精暴露的后果的变化，是关键的研究目标。非人灵长类动物为这类转化研究提供了最佳模型。非人类灵长类动物表现出根深蒂固的，滥用的饮酒模式，这是人类酗酒的特征，但它们也表现出饮酒模式的变化。我们建议使用这个模型，沿着从多个实验测试得出的情感和行为概况，以确定候选预测因素过量饮酒。使用纵向设计，以及组间分析，我们广泛的目的是检查行为和生理相关的脆弱性（或弹性）滥用模式的乙醇消费和 确定饮酒对四个关键目标的影响（冲动/新奇寻求/抑制控制;记忆和认知;心脏信号动力学;月经周期）。最后，我们将描述一个急性期的戒断行为体征和心律失常，并将这些变化与个人的酒精摄入模式。具体的空气是 1)研究气质的核心方面（冲动性，新奇寻求，抑制控制），记忆，认知和个体过度饮酒自我管理风险之间的关系。 2)确定固定剂量（诱导）和随意自我给药（1年）酒精对气质、记忆和认知的影响。 3)确定固定剂量和长期自我饮酒对心脏和神经内分泌功能的影响。 4)描述长期（12个月）酒精自我给药后戒断（24小时）的行为和生理后遗症

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