Ontogeny of Physical versus Emotional Stress and Reward Pathways

描述(由研究人员提供)：早期生活经历对个人健康有深远影响。身体和/或精神上的虐待会导致一种负面的幸福感，包括终生持续的行为问题。据估计，有身体和/或情感忽视史的青少年和成年人可能会出现药物滥用、焦虑和严重抑郁。虽然情感成本无法衡量，但社会的经济成本估计为960亿美元/年。虽然压力反应的机制在很大程度上是以成年人为特征的，但人们对早期身体或情绪压力的神经生物学后果及其长期后果知之甚少。这些观察结果强调了更好地了解早期生活应激的神经生物学及其终生影响的必要性。这项建议的目的是研究大脑的食欲神经回路在压力的长期行为和生化后果中的作用，使用身体(轻微的足部电击)和情感(见证足部电击)压力的啮齿动物模型。这种方法是新颖的，因为它集中在大脑中对动机、奖励和精神运动活动至关重要的食欲区域(伏隔核和VTA)。目的1利用旨在评估动物情感状态的行为测试，检查一生中暴露在身体或情绪压力下是否影响情绪反应，这些测试包括评估对：(A)滥用药物(可卡因、吗啡)、(B)自然回报(蔗糖)和(C)对引发焦虑的情况的反应(野外)和其他应激源(强迫游泳压力)的敏感性。目的2使用蛋白质生物化学方法，在身体/情绪应激后，评估这一回路的生化完整性。这将允许识别受任何一种形式的压力以及年龄调节的基因产物，从而为未来的实验奠定基础，在这些实验中，这些识别出的与压力相关的蛋白质将被包装到病毒载体中，研究它们如何影响发育中的大脑，导致适应增加对滥用药物和其他行为障碍的易感性。所获得的数据将提高我们对身体和情绪压力在早期发展中所起的作用的理解，这些压力在后来的生活中调节病理行为。公共卫生相关性：儿童时期有身体和/或情感忽视史的青少年和成年人可能会患上药物滥用、焦虑和严重的抑郁障碍。尽管对社会造成的经济损失估计为每年960亿美元，但人们对早年身体或情绪压力的神经生物学后果及其长期后果知之甚少。这些观察结果强调了更好地了解早期生活应激的神经生物学及其终生影响的必要性。

DESCRIPTION (provided by investigator): Early-life experiences have profound effects on an individual's health. Physical and/or emotional abuse can lead to a negative sense of well-being, including behavioral problems that continue throughout life. It is estimated that youngsters and adults with history of physical and/or emotional neglect are likely to develop substance abuse, anxiety, and major depression. Though the emotional cost cannot be measured, the economic cost to society is estimated at $96 billion/year. While the mechanisms of stress response have been largely characterized in adults, little is known about the neurobiological consequences of early-life physical or emotional stress and its long-term consequences. These observations underscore the need for better understanding of the neurobiology of early-life stress and its life-long effects. The goal of this proposal is to study the role of brain's appetitive neural circuits in the long-term behavioral and biochemical consequences of stress, using a rodent model of physical (mild foot shock) versus emotional (witness foot shock) stress. This approach is novel because it focuses on appetitive regions of the brain (the nucleus accumbens and the VTA) important for motivation, reward, and psychomotor activity. Aim 1 examines whether exposure to physical or emotional stress during the life-span influences emotional reactivity using behavioral tests designed to assess an animal's affective state, these include assessing sensitivity to: (a) drugs of abuse (cocaine, morphine), (b) natural rewards (sucrose), and (c) reactivity to anxiety-eliciting situations (open-field), and other stressors (forced swim stress). Aim 2 assesses the biochemical integrity of this circuit, using protein biochemistry, after physical/emotional stress. This will allow for identification of gene products regulated by either form of stress, and by age, thus setting the stage for future experiments in which these identified 'stress- related' proteins will be packaged into viral vectors to study how they affect developing brain, resulting in adaptations that increase vulnerability to drugs of abuse and other behavioral disorders. Data obtained will improve our understanding of the role physical and emotional stress plays in early development in mediating pathological behavior later in life. PUBLIC HEALTH RELEVANCE: Youngsters and adults with childhood history of physical and/or emotional neglect are likely to develop substance abuse, anxiety, and major depression disorders. Though the economic cost to society is estimated at $96 billion/year, little is known about the neurobiological consequences of early-life physical or emotional stress and its long-term consequences. These observations underscore the need for better understanding of the neurobiology of early-life stress and its life-long effects.