FETAL ALCOHOL EFFECTS IN MONKEYS: DOPAMINE AND BEHAVIOR

胎儿酒精对猴子的影响：多巴胺和行为

• 批准号: 6754500
• 负责人: MARY L SCHNEIDER
• 金额: $ 40.03万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-08-01 至 2006-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6754500
• 关键词: Macaca mulatta; alcoholic beverage consumption; attention deficit disorder; behavior test; behavioral /social science research tag; brain imaging /visualization /scanning; disease /disorder model; dopamine; dopamine receptor; embryo /fetus toxicology; fetal alcohol syndrome; habits; learning; longitudinal animal study; magnetic resonance imaging; mental retardation; methylphenidate; neuropsychological tests; neurotransmitter biosynthesis; positron emission tomography; pregnancy; psychological stressor; receptor binding; videotape /videodisc

Fetal alcohol syndrome, (FAS) is the leading known cause of mental retardation today and currently represents an enormous problem for our society. The central question addressed by this proposal is whether moderate alcohol exposure constitutes a danger to the developing offspring. To address this issue, we propose to assess the behavior and physiology in 50 monkeys from four conditions: 1) mothers consumed moderate level alcohol daily throughout pregnancy 2) mothers experienced psychological stress; 3) mothers consumed moderate level alcohol and experienced psychological stress; and 4) mothers consumed sucrose (controls) (Schneider et al., 1997). The specific aims are as follows: 1) to characterize dopamine D2 receptor densities in striata of offspring using in vivo PET imaging techniques 2) to characterize dopamine synthesis in these same cohorts, also using PET imaging, and to uncouple presynaptic synthesis of dopamine from postsynaptic receptor binding availability; 3) to evaluate these monkeys with a standard battery of widely accepted tests and measurements, which index cognitive functioning and behavior; and 4) to determine the effects of a dopamine agonist, methylphenidate, on behavior and cognitive performance in this cohort of monkeys. Our primate model has allowed control of the exact timing and level of alcohol exposure to the fetus and the separation of the effects of alcohol from other life-style factors, such as psychological stress The proposed studies provide a unique and unprecedented opportunity not only to better understand the underlying neurobiology of fetal alcohol effects, but also to discover potential in vivo diagnostic markers for detecting fetal alcohol- induced brain damage. Increasing our understanding of the association between behavior, cognition, and molecular mechanisms of neuronal function in fetal alcohol-exposed primates could aid in early identification and appropriate treatment of children with prenatal alcohol exposure.

胎儿酒精综合症（FAS）是当今已知的导致智力低下的主要原因，目前对我们的社会来说是一个巨大的问题。 该提案解决的核心问题是适度饮酒是否会对发育中的后代构成危险。 为了解决这个问题，我们建议从四种情况下评估 50 只猴子的行为和生理机能：1) 母亲在整个怀孕期间每天饮用适量酒精；2) 母亲经历过心理压力； 3）母亲饮酒适量，心理压力大； 4) 母亲食用蔗糖（对照）（Schneider 等，1997）。具体目标如下：1) 使用体内 PET 成像技术表征后代纹状体中的多巴胺 D2 受体密度 2) 也使用 PET 成像来表征这些同一队列中的多巴胺合成，并将突触前合成与突触后解耦。受体结合可用性； 3）通过一系列广泛接受的标准测试和测量来评估这些猴子，这些测试和测量反映了认知功能和行为； 4) 确定多巴胺激动剂哌甲酯对这组猴子的行为和认知表现的影响。我们的灵长类动物模型可以控制胎儿接触酒精的确切时间和水平，并将酒精的影响与其他生活方式因素（例如心理压力）分开。拟议的研究提供了一个独特且前所未有的机会，不仅可以更好地了解胎儿酒精影响的潜在神经生物学，同时也发现潜在的体内诊断标记物，用于检测胎儿酒精引起的脑损伤。 增加我们对胎儿酒精暴露灵长类动物的行为、认知和神经元功能分子机制之间关系的了解，有助于早期识别和适当治疗产前酒精暴露的儿童。