Abstract:
Addiction is a chronic relapsing disorder with devastating personal, societal, and economic consequences. In humans, early-life adversity (ELA) such as trauma, neglect, and resource scarcity are linked with increased risk of later-life addiction, but the brain mechanisms underlying this link are still poorly understood. Here, we focus on data from rodent models of ELA and addiction, in which causal effects of ELA on later-life responses to drugs and the neurodevelopmental mechanisms by which ELA increases vulnerability to addiction can be determined. We first summarize evidence for a link between ELA and addiction in humans, then describe how ELA is commonly modeled in rodents. Since addiction is a heterogeneous disease with many individually varying behavioral aspects that may be impacted by ELA, we next discuss common rodent assays of addiction-like behaviors. We then summarize the specific addiction-relevant behavioral phenotypes caused by ELA in male and female rodents and discuss some of the underlying changes in brain reward and stress circuits that are likely responsible. By better understanding the behavioral and neural mechanisms by which ELA promotes addiction vulnerability, we hope to facilitate development of new approaches for preventing or treating addiction in those with a history of ELA.
摘要:
成瘾是一种慢性复发性疾病,具有毁灭性的个人,社会,和经济后果。在人类中,早期生活逆境(ELA),如创伤,疏忽,资源稀缺与晚年成瘾的风险增加有关,但是这种联系背后的大脑机制仍然知之甚少。这里,我们专注于来自ELA和成瘾的啮齿动物模型的数据,可以确定ELA对晚年对药物的反应的因果效应以及ELA增加成瘾易感性的神经发育机制。我们首先总结了ELA与人类成瘾之间联系的证据,然后描述ELA通常是如何在啮齿动物中建模的。由于成瘾是一种异质性疾病,有许多个体不同的行为方面可能受到ELA的影响,我们接下来讨论常见的啮齿动物成瘾样行为的检测。然后,我们总结了ELA在雄性和雌性啮齿动物中引起的特定成瘾相关行为表型,并讨论了可能负责的大脑奖励和压力回路的一些潜在变化。通过更好地了解ELA促进成瘾脆弱性的行为和神经机制,我们希望促进开发预防或治疗有ELA病史的成瘾的新方法。