Ross Emily J, Graham Devon L, Money Kelli M, Stanwood Gregg D
Chemical & Physical Biology Program, Vanderbilt University, Nashville, TN, USA.
Department of Pharmacology, Vanderbilt University, Nashville, TN, USA.
Neuropsychopharmacology. 2015 Jan;40(1):61-87. doi: 10.1038/npp.2014.147. Epub 2014 Jun 18.
Most drugs of abuse easily cross the placenta and can affect fetal brain development. In utero exposures to drugs thus can have long-lasting implications for brain structure and function. These effects on the developing nervous system, before homeostatic regulatory mechanisms are properly calibrated, often differ from their effects on mature systems. In this review, we describe current knowledge on how alcohol, nicotine, cocaine, amphetamine, Ecstasy, and opiates (among other drugs) produce alterations in neurodevelopmental trajectory. We focus both on animal models and available clinical and imaging data from cross-sectional and longitudinal human studies. Early studies of fetal exposures focused on classic teratological methods that are insufficient for revealing more subtle effects that are nevertheless very behaviorally relevant. Modern mechanistic approaches have informed us greatly as to how to potentially ameliorate the induced deficits in brain formation and function, but conclude that better delineation of sensitive periods, dose-response relationships, and long-term longitudinal studies assessing future risk of offspring to exhibit learning disabilities, mental health disorders, and limited neural adaptations are crucial to limit the societal impact of these exposures.
大多数滥用药物很容易穿过胎盘，会影响胎儿大脑发育。因此，子宫内接触药物会对大脑结构和功能产生长期影响。在稳态调节机制尚未正确校准之前，这些对发育中神经系统的影响通常与它们对成熟系统的影响不同。在这篇综述中，我们描述了关于酒精、尼古丁、可卡因、安非他命、摇头丸和阿片类药物（以及其他药物）如何改变神经发育轨迹的现有知识。我们既关注动物模型，也关注来自横断面和纵向人体研究的现有临床和影像学数据。早期关于胎儿接触药物的研究集中在经典的致畸学方法上，这些方法不足以揭示那些虽然微妙但与行为密切相关的影响。现代机制研究方法让我们对如何潜在改善大脑形成和功能方面的诱导缺陷有了很多了解，但得出的结论是，更好地界定敏感期、剂量反应关系，以及评估后代未来出现学习障碍、心理健康障碍和有限神经适应风险的长期纵向研究，对于限制这些接触对社会的影响至关重要。
