Plasticity of the Reward Circuitry After Early-Life Adversity: Mechanisms and Significance

被引:71
作者
Birnie, Matthew T. [1 ]
Kooiker, Cassandra L. [2 ]
Short, Annabel K. [1 ]
Bolton, Jessica L. [1 ]
Chen, Yuncai [1 ]
Baram, Tallie Z. [1 ,2 ]
机构
[1] Univ Calif Irvine, Dept Pediat, Sch Med, Irvine, CA 92697 USA
[2] Univ Calif Irvine, Dept Anat & Neurobiol, Sch Med, Irvine, CA 92717 USA
基金
美国国家卫生研究院;
关键词
Addiction; Amygdala; Anhedonia; CRH; Nucleus accumbens; Stress; CORTICOTROPIN-RELEASING-FACTOR; NUCLEUS-ACCUMBENS SHELL; MEDIAL PREFRONTAL CORTEX; ANXIETY-LIKE BEHAVIOR; D1; DOPAMINE-RECEPTOR; MATERNAL SEPARATION; ENVIRONMENT INTERACTIONS; EXCITATORY TRANSMISSION; SEROTONIN TRANSPORTER; FEEDING-BEHAVIOR;
D O I
10.1016/j.biopsych.2019.12.018
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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.
引用
收藏
页码:875 / 884
页数:10
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