Medical Scientist Training Program, University of Miami Miller School of Medicine, Miami, FL 33136, USA; Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, FL 33136, USA; Department of Surgery, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
Exp Neurol. 2021 May;339:113621. doi: 10.1016/j.expneurol.2021.113621. Epub 2021 Jan 29.
The heightened incidence of opioid use during pregnancy has resulted in unprecedented rates of neonates prenatally exposed to opioids. Prenatal opioid exposure (POE) results in significantly adverse medical, developmental, and behavioral outcomes in offspring. Of growing interest is whether POE contributes to future vulnerability to substance use disorders. The effects of POE on brain development is difficult to assess in humans, as the timing, dose, and route of drug exposure together with complex genetic and environmental factors affect susceptibility to addiction. Preclinical models of POE have allowed us to avoid methodological difficulties and confounding factors of POE in humans. Here, we review the effects of maternal opioid exposure on the developing brain with an emphasis on the neurobiological basis of drug addiction and on preclinical models of POE and their limitations. These studies have indicated that POE increases self-administration of drugs, reward-driven behaviors in the conditioned place paradigm, and locomotor sensitization. While addiction is multifaceted and vulnerability to drug addiction is still inconclusive in human studies of prenatally exposed infants, animal studies do provide a noteworthy corroboration of negative behavioral outcomes.
孕期阿片类药物使用的发生率升高,导致新生儿产前暴露于阿片类药物的比例前所未有。产前阿片类药物暴露(POE)会导致后代出现显著的医疗、发育和行为结果不良。越来越引起关注的是,POE 是否会导致未来对物质使用障碍的易感性。由于药物暴露的时间、剂量和途径以及复杂的遗传和环境因素共同影响成瘾的易感性,因此很难在人类中评估 POE 对大脑发育的影响。POE 的临床前模型使我们能够避免人类 POE 中的方法学困难和混杂因素。在这里,我们重点讨论了母体阿片类药物暴露对发育中大脑的影响,强调了药物成瘾的神经生物学基础以及 POE 的临床前模型及其局限性。这些研究表明,POE 会增加自我给药、条件性位置偏好范式中的奖励驱动行为以及运动敏化。虽然成瘾是多方面的,并且在产前暴露于婴儿的人类研究中对药物成瘾的易感性仍不确定,但动物研究确实为不良行为结果提供了值得注意的佐证。