Ontogeny of Physical versus Emotional Stress and Reward Pathways

描述（由研究者提供）：早期生活经历对个体的健康有深远的影响。身体和/或情感虐待会导致消极的幸福感，包括终身持续的行为问题。据估计，有身体和/或情感忽视史的青少年和成年人可能会发展成药物滥用、焦虑和重度抑郁症。虽然情感成本无法衡量，但社会的经济成本估计为每年960亿美元。虽然压力反应的机制在很大程度上是在成年人的特点，很少有人知道的神经生物学后果的早期生活的身体或情绪压力及其长期后果。这些观察结果强调，需要更好地了解早期生活压力的神经生物学及其终身影响。这项计划的目的是研究大脑的食欲神经回路在长期的行为和生化后果的压力，使用啮齿动物模型的物理（轻度脚休克）与情感（证人脚休克）的压力。这种方法是新颖的，因为它关注的是大脑中对动机、奖励和精神活动很重要的食欲区域（延髓核和腹侧被盖区）。目的1使用旨在评估动物情感状态的行为测试来检查在寿命期间暴露于身体或情感压力是否影响情感反应，这些测试包括评估对以下的敏感性：（a）滥用药物（可卡因，吗啡），（B）自然奖励（蔗糖），和（c）对引发焦虑的情况（开阔场地）和其他压力源（强迫游泳压力）的反应。目的2评估的生化完整性，使用蛋白质生物化学，在身体/情绪压力。这将允许识别由任何形式的压力和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，这些识别的“压力相关”蛋白将被包装到病毒载体中，以研究它们如何影响发育中的大脑，导致适应性增加对滥用药物和其他行为障碍的脆弱性。所获得的数据将提高我们对身体和情绪压力在早期发育中介导晚年病理行为的作用的理解。公共卫生相关性：青少年和成年人的身体和/或情感忽视的童年历史很可能发展药物滥用，焦虑和严重抑郁症。虽然社会的经济成本估计为960亿美元/年，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，需要更好地了解早期生活压力的神经生物学及其终身影响。

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.