Fetal Alcohol Effects in Monkeys: Dopamine and Behavior

胎儿酒精对猴子的影响：多巴胺和行为

基本信息

批准号：
7845584
负责人：
MARY L SCHNEIDER
金额：
$ 61.79万
依托单位：
UNIVERSITY OF WISCONSIN-MADISON
依托单位国家：
美国
项目类别：
财政年份：
2001
资助国家：
美国
起止时间：
2001-08-01 至 2011-09-14
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7845584
关键词：
Address Adolescence Adult Alcohol consumption Alcohol-Related Neurodevelopmental Disorder Alcohols Alleles Attention Behavior Behavioral Binding Binding Sites Birth Brain Brain region Cerebrum Chemicals Child Clinical Cognition Cognitive Control Animal Corpus striatum structure DRD2 gene Data Development Dopamine Dopamine D1 Receptor Dopamine D2 Receptor Dose Early identification Educational Intervention Environment Evaluation Exposure to Fetal Alcohol Exposure Fetal alcohol effects Fetus Frequencies Genetic Variation Human Image Impairment Infant Intervention Lead Life Style Macaca mulatta Measures Mediating Metabolism Methylphenidate Modeling Monkeys Mothers Motor Neonatal Neurobiology Nucleus Accumbens Outcome Pathway interactions Performance Phase Physiological Positron-Emission Tomography Prefrontal Cortex Pregnancy Prevention strategy Primates Process Psychological Stress Rattus Regulation Reporting Research Research Personnel Risk Rodent Role Screening procedure Sensory Solutions Sorting - Cell Movement Stimulus Stress Stressful Event Sucrose Synapses System Tactile Testing Time Tracer Ventral Striatum Wisconsin Work alcohol effect alcohol exposure base behavior measurement biological adaptation to stress cohort dopamine system dopamine transporter emerging adult executive function experience fetal fluorodeoxyglucose follow-up frontal lobe glucose analog glucose metabolism hypothalamic-pituitary-adrenal axis in utero infant temperament innovation insight longitudinal design mRNA Expression neurobehavior neurobehavioral postnatal postsynaptic prenatal stress prepulse inhibition presynaptic programs prospective psychologic putamen receptor receptor binding sensory stimulus serotonin transporter uptake

项目摘要

DESCRIPTION (provided by applicant): AA12277 has supported an ongoing prospective longitudinal primate study to increase our understanding of the mechanisms underlying prenatal stress and moderate level prenatal alcohol exposure effects. The primate model has allowed control of the exact timing and level of prenatal stress and fetal alcohol exposure to the fetus and the separation of effects of alcohol and prenatal stress and from other life-style factors. The primary hypothesis is that stress and/or alcohol in utero alters the development of the dopamine (DA) system and the normal development of neurobehavior, stress responses, and executive function. This continuation project will focus on 50 monkeys from four conditions: 1) mothers experienced psychological stress during pregnancy; 2) mothers consumed daily moderate dose alcohol during pregnancy; 3) mothers consumed alcohol and experienced psychological stress (as above); and 4) mothers consumed sucrose solution (controls). These monkeys have been followed since birth and have been well-characterized behaviorally. PET studies showed that prenatal stress and fetal alcohol exposure altered D2 receptor binding/DA synthesis and that fetal alcohol effects on the DA system depended upon the timing and duration of alcohol exposure. Specific Aim 1 will assess D1 receptor binding in the prefrontal cortex, nucleus accumbens, putamen and caudate and cognitive performance dependent on DAergic function. Specific Aim 2 will assess the binding of DA transporters in these same striatal and extrastriatal regions. Specific Aim 3 will examine cerebral FDG metabolism in the prefrontal cortex during cognitive testing versus a control state to examine brain systems under dynamic conditions. Specific Aim 4 will examine prepulse inhibition and habituation to repeated tactile stimuli based on the role of DAergic pathways underlying sensorimotor gating as well as clinical evidence of unusual sensory sensitivities in children with fetal alcohol exposure. The scientific significance of this work will increase our understanding of brain abnormalities and neurobiological pathways underlying prenatal stress and/or fetal alcohol-induced impairments in cognition and behavior. The clinical importance of this longitudinal research is that it may lead to innovative models for screening tests and interventions that may facilitate early identification and the development of effective clinical and educational interventions for children at risk for prenatal stress and/or alcohol-related neurodevelopmental disorders.

描述（由申请人提供）：AA12277 支持一项正在进行的前瞻性纵向灵长类动物研究，以增进我们对产前压力和中等水平产前酒精暴露影响的机制的理解。灵长类动物模型可以控制胎儿的产前压力和胎儿酒精暴露的确切时间和水平，并将酒精和产前压力的影响与其他生活方式因素分开。主要假设是子宫内的压力和/或酒精会改变多巴胺 (DA) 系统的发育以及神经行为、压力反应和执行功能的正常发育。这个延续项目将重点关注 50 只猴子，它们有四种情况：1）母亲在怀孕期间经历过心理压力； 2) 母亲在怀孕期间每天饮用适量酒精； 3）母亲饮酒并经历心理压力（如上所述）； 4) 母亲饮用蔗糖溶液（对照）。这些猴子从出生起就受到跟踪，并且其行为特征得到了很好的表征。 PET 研究表明，产前应激和胎儿酒精暴露会改变 D2 受体结合/DA 合成，并且胎儿酒精对 DA 系统的影响取决于酒精暴露的时间和持续时间。具体目标 1 将评估前额皮质、伏核、壳核和尾状核中 D1 受体的结合以及依赖于 DAergic 功能的认知表现。具体目标 2 将评估 DA 转运蛋白在这些相同纹状体和纹状体外区域的结合。具体目标 3 将在认知测试期间检查前额皮质中的大脑 FDG 代谢，并与控制状态进行比较，以检查动态条件下的大脑系统。具体目标 4 将根据感觉运动门控中 DAergic 通路的作用以及胎儿酒精暴露儿童异常感觉敏感性的临床证据，检查前脉冲抑制和对重复触觉刺激的习惯。这项工作的科学意义将增加我们对产前压力和/或胎儿酒精引起的认知和行为障碍的大脑异常和神经生物学途径的理解。这项纵向研究的临床重要性在于，它可能会带来筛查测试和干预措施的创新模型，从而有助于对有产前应激和/或酒精相关神经发育障碍风险的儿童进行早期识别和制定有效的临床和教育干预措施。