Department of Pediatrics, School of Medicine, University of California, Irvine, Irvine, California.
Department of Anatomy and Neurobiology, School of Medicine, University of California, Irvine, Irvine, California.
Biol Psychiatry. 2020 May 15;87(10):875-884. doi: 10.1016/j.biopsych.2019.12.018. Epub 2019 Dec 24.
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.
奖励回路的功能紊乱是许多情感障碍的基础。这种功能紊乱可能表现为异常行为，包括冒险行为、抑郁、快感缺失和成瘾。生命早期逆境是涉及奖励回路的青少年和成人情感障碍的常见前兆。然而，生命早期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，我们使用动物模型中的前沿技术提供了新的信息，以剖析生命早期逆境引发应激和奖励回路复杂相互作用失调的机制。我们提出，奖励回路中某些分子定义的途径特别容易受到生命早期逆境的影响。我们检查了表达应激敏感肽促肾上腺皮质释放因子 (CRF)的区域和途径，CRF 已在奖励回路和相互作用的应激回路的关键组成部分中被鉴定出来。值得注意的是，CRF 在这些大脑区域中的几个区域中受到生命早期逆境的强烈调节。我们专注于杏仁核核及其投射，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/焦虑区域连接增强的基础，破坏了这个关键愉悦和奖励位置的功能。
