Disrupted operation of the reward circuitry underlies many aspects of affective disorders. Such disruption may manifest as aberrant behavior including risk taking, depression, anhedonia, and addiction. Early-life adversity is a common antecedent of adolescent and adult affective disorders involving the reward circuitry. However, whether early-life adversity influences the maturation and operations of the reward circuitry, and the potential underlying mechanisms, remain unclear. Here, we present novel information using cutting-edge technologies in animal models to dissect out the mechanisms by which early-life adversity provokes dysregulation of the complex interactions of stress and reward circuitries. We propose that certain molecularly defined pathways within the reward circuitry are particularly susceptible to early-life adversity. We examine regions and pathways expressing the stress-sensitive peptide corticotropin-releasing factor (CRF), which has been identified in critical components of the reward circuitry and interacting stress circuits. Notably, CRF is strongly modulated by early-life adversity in several of these brain regions. Focusing on amygdala nuclei and their projections, we provide evidence suggesting that aberrant CRF expression and function may underlie augmented connectivity of the nucleus accumbens with fear/anxiety regions, disrupting the function of this critical locus of pleasure and reward.

中文翻译：

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早期生活逆境后奖励回路的可塑性：机制和意义

奖励回路的中断运行是情感障碍的许多方面的基础。这种破坏可能表现为异常行为，包括冒险、抑郁、快感缺乏和成瘾。早年逆境是涉及奖赏回路的青少年和成人情感障碍的常见前因。然而，早期生活中的逆境是否会影响奖励回路的成熟和运作，以及潜在的潜在机制，仍不清楚。在这里，我们在动物模型中使用尖端技术提供新信息，以剖析早期生活逆境引起压力和奖励回路复杂相互作用失调的机制。我们建议奖励回路中某些分子定义的途径特别容易受到早期逆境的影响。我们检查了表达压力敏感肽促肾上腺皮质激素释放因子 (CRF) 的区域和通路，该因子已在奖励回路和相互作用压力回路的关键组件中得到鉴定。值得注意的是，CRF 在这些大脑区域中的几个区域中受到早期逆境的强烈调节。专注于杏仁核及其预测，我们提供的证据表明，异常的 CRF 表达和功能可能是伏隔核与恐惧/焦虑区域增强连接的基础，破坏了这一关键的愉悦和奖励位点的功能。CRF 在这些大脑区域中的几个区域中受到早期逆境的强烈调节。关注杏仁核及其预测，我们提供的证据表明，异常的 CRF 表达和功能可能是伏隔核与恐惧/焦虑区域增强连接的基础，破坏了这一关键的快乐和奖励位点的功能。CRF 在这些大脑区域中的几个区域中受到早期逆境的强烈调节。专注于杏仁核及其预测，我们提供的证据表明，异常的 CRF 表达和功能可能是伏隔核与恐惧/焦虑区域增强连接的基础，破坏了这一关键的愉悦和奖励位点的功能。