Prescription opioid abuse during and after pregnancy is a rising public health concern. While earlier studies have documented that offspring exposed to opioids in utero have impaired neurodevelopment, a significant knowledge gap remains in comparing the overall development between offspring exposed in utero and postnatally. Adding a layer of complexity is the role of heredity in the overall development of these exposed offspring. To fill in these important knowledge gaps, the current study uses a preclinical rat model mimicking oxycodone (oxy) exposure in utero (IUO) and postnatally (PNO) to investigate comparative and intergenerational effects in the two different treatment groups. While significant phenotypic attributes were observed with the two treatments and across the two generations, RNA sequencing revealed alterations in the expression of key synaptic genes in the two exposed groups in both generations. RNA sequencing and post validation of genes using RT-PCR highlighted the differential expression of several neuropeptides associated with the hypocretin system, a system recently implicated in addiction. Further, behavior studies revealed anxiety-like behaviors and social deficits that persisted even in the subsequent generations in the two treatment groups. To summarize, our study for the first time reveals a new line of investigation on the potential risks associated with oxy use during and after pregnancy, specifically the disruption of neurodevelopment and intergenerational impact on behavior.

怀孕期间和之后的处方阿片类药物滥用是一个日益严重的公共卫生问题。虽然早期的研究表明，在子宫内暴露于阿片类药物的后代会损害神经发育，但在比较子宫内和出生后暴露的后代之间的整体发育情况方面仍然存在重大的知识差距。增加一层复杂性是遗传在这些暴露后代的整体发展中的作用。为了填补这些重要的知识空白，目前的研究使用模拟子宫内 (IUO) 和出生后 (PNO) 羟考酮 (oxy) 暴露的临床前大鼠模型来研究两个不同治疗组的比较和代际影响。虽然在两个处理和两代之间观察到显着的表型属性，RNA 测序揭示了两代暴露组中关键突触基因表达的改变。使用 RT-PCR 对基因进行 RNA 测序和后验证强调了与下丘脑分泌素系统相关的几种神经肽的差异表达，该系统最近与成瘾有关。此外，行为研究揭示了焦虑样行为和社交缺陷，即使在两个治疗组的后代中也持续存在。总而言之，我们的研究首次揭示了与怀孕期间和之后使用氧气相关的潜在风险的新调查线，特别是神经发育的破坏和对行为的代际影响。使用 RT-PCR 对基因进行 RNA 测序和后验证强调了与下丘脑分泌素系统相关的几种神经肽的差异表达，该系统最近与成瘾有关。此外，行为研究揭示了焦虑样行为和社交缺陷，即使在两个治疗组的后代中也持续存在。总而言之，我们的研究首次揭示了与怀孕期间和之后使用氧气相关的潜在风险的新调查线，特别是神经发育的破坏和对行为的代际影响。使用 RT-PCR 对基因进行 RNA 测序和后验证强调了与下丘脑分泌素系统相关的几种神经肽的差异表达，该系统最近与成瘾有关。此外，行为研究揭示了焦虑样行为和社交缺陷，即使在两个治疗组的后代中也持续存在。总而言之，我们的研究首次揭示了与怀孕期间和之后使用氧气相关的潜在风险的新调查线，特别是神经发育的破坏和对行为的代际影响。行为研究揭示了类似焦虑的行为和社交缺陷，即使在两个治疗组的后代中也持续存在。总而言之，我们的研究首次揭示了与怀孕期间和之后使用氧气相关的潜在风险的新调查线，特别是神经发育的破坏和对行为的代际影响。行为研究揭示了类似焦虑的行为和社交缺陷，即使在两个治疗组的后代中也持续存在。总而言之，我们的研究首次揭示了与怀孕期间和之后使用氧气相关的潜在风险的新调查线，特别是神经发育的破坏和对行为的代际影响。