Department of Psychology, Wayne State University, Detroit, MI, 48202, USA.
Dept of Behavioral Neuroscience and Psychiatry, Wayne State University, Detroit, MI, 48202, USA.
Neuropharmacology. 2024 Oct 1;257:110060. doi: 10.1016/j.neuropharm.2024.110060. Epub 2024 Jul 1.
The escalating incidence of opioid-related issues among pregnant women in the United States underscores the critical necessity to understand the effects of opioid use and Medication for Opioid Use Disorders (MOUDs) during pregnancy. This research employed a translational rodent model to examine the impact of gestational exposure to buprenorphine (BUP) or morphine on maternal behaviors and offspring well-being. Female rats received BUP or morphine before conception, representing established use, with exposure continuing until postnatal day 2 or discontinued on gestational day 19 to mimic treatment cessation before birth. Maternal behaviors - including care, pup retrieval, and preference - as well as hunting behaviors and brain neurotransmitter levels were assessed. Offspring were evaluated for mortality, weight, length, milk bands, surface righting latency, withdrawal symptoms, and brain neurotransmitter levels. Our results reveal that regardless of exposure length (i.e., continued or discontinued), BUP resulted in reduced maternal care in contrast to morphine-exposed and control dams. Opioid exposure altered brain monoamine levels in the dams and offspring, and was associated with increased neonatal mortality, reduced offspring weight, and elevated withdrawal symptoms compared to controls. These findings underscore BUP's potential disruption of maternal care, contributing to increased pup mortality and altered neurodevelopmental outcomes in the offspring. This study calls for more comprehensive research into prenatal BUP exposure effects on the maternal brain and infant development with the aim to mitigate adverse outcomes in humans exposed to opioids during pregnancy.
在美国,与阿片类药物相关的问题在孕妇中的发生率不断上升,这突显出迫切需要了解阿片类药物使用和阿片类药物使用障碍(MOUD)治疗在怀孕期间的影响。本研究采用转化啮齿动物模型来研究母体在怀孕期间接触丁丙诺啡(BUP)或吗啡对母体行为和后代健康的影响。雌性大鼠在受孕前接受 BUP 或吗啡治疗,代表已建立的使用,暴露持续到产后第 2 天或在妊娠第 19 天停止,以模拟出生前的治疗停止。评估了母体行为,包括护理、幼崽回收和偏好,以及狩猎行为和大脑神经递质水平。评估了后代的死亡率、体重、长度、乳带、表面翻身潜伏期、戒断症状和大脑神经递质水平。我们的结果表明,无论暴露时间长短(即持续或停止),BUP 导致母体护理减少,与吗啡暴露和对照母鼠相比。阿片类药物暴露改变了母体和后代的大脑单胺水平,并与新生儿死亡率增加、后代体重减轻和戒断症状升高有关,与对照组相比。这些发现强调了 BUP 对母体护理的潜在干扰,导致幼崽死亡率增加和后代神经发育结果改变。这项研究呼吁对产前 BUP 暴露对母体大脑和婴儿发育的影响进行更全面的研究,以期减轻孕妇暴露于阿片类药物的不良后果。