Section of Forensic Research, Department of Forensic Sciences, Oslo University Hospital, P.O. Box 4950 Nydalen, Oslo 0424, Norway; Department of Pharmacy, Faculty of Mathematics and Natural Sciences, University of Oslo, P.O. Box 1068 Blindern, Oslo 0316, Norway.
Section of Forensic Research, Department of Forensic Sciences, Oslo University Hospital, P.O. Box 4950 Nydalen, Oslo 0424, Norway; Department of Pharmacy, Faculty of Mathematics and Natural Sciences, University of Oslo, P.O. Box 1068 Blindern, Oslo 0316, Norway.
Drug Alcohol Depend. 2024 Sep 1;262:111367. doi: 10.1016/j.drugalcdep.2024.111367. Epub 2024 Jun 12.
The use of medications for opioid use disorder such as methadone or buprenorphine is increasing among pregnant women. However, long-term effects of this treatment on the children's health are not well understood. A key challenge is distinguishing the effects of opioid exposure from other confounding factors associated with human opioid use, such as reduced maternal care. In this study, we therefore used a multi-risk factor design to examine anxiety-like behavior in rats prenatally exposed to methadone or buprenorphine, with or without maternal separation the first two weeks after birth.
Female Sprague Dawley rats were exposed to methadone (10mg/kg/day), buprenorphine (1mg/kg/day) or sterile water throughout gestation. Half of the offspring in each litter experienced maternal separation for 3h per day from postnatal day 2 to 12. Male and female offspring (6-9 weeks) were tested in the open field, light-dark transition and elevated plus maze tests to assess anxiety-like behavior.
Offspring exposed to buprenorphine and not subjected to maternal separation displayed increased anxiety-like behavior in 3 out of 6 outcomes in the light-dark transition and elevated plus maze tests. Maternal separation did not exacerbate, but rather diminished this behavior. Males and females responded differently to methadone, with a trend towards reduced anxiety for males and increased anxiety for females.
Prenatal exposure to methadone or buprenorphine may increase the risk of developing anxiety-like behavior later in life, but the effect depends on specific subgroup characteristics. Further research is required to draw definitive conclusions.
在孕妇中，使用美沙酮或丁丙诺啡等药物治疗阿片类药物使用障碍的情况正在增加。然而，这种治疗对儿童健康的长期影响还不是很清楚。一个关键的挑战是区分阿片类药物暴露的影响与与人类阿片类药物使用相关的其他混杂因素，如减少母婴护理。在这项研究中，我们因此使用了多风险因素设计，来研究产前暴露于美沙酮或丁丙诺啡的大鼠的焦虑样行为，同时考虑了出生后前两周的母婴分离。
雌性 Sprague Dawley 大鼠在整个妊娠期接受美沙酮（10mg/kg/天）、丁丙诺啡（1mg/kg/天）或无菌水。每个窝的一半幼崽在出生后第 2 天至第 12 天每天接受 3 小时的母婴分离。雄性和雌性幼崽（6-9 周）在旷场、明暗过渡和高架十字迷宫测试中进行测试，以评估焦虑样行为。
暴露于丁丙诺啡且未经历母婴分离的幼崽在明暗过渡和高架十字迷宫测试的 6 个结果中的 3 个中表现出焦虑样行为增加。母婴分离并没有加剧，而是减轻了这种行为。雄性和雌性对美沙酮的反应不同，雄性表现出焦虑减少的趋势，而雌性表现出焦虑增加的趋势。
产前暴露于美沙酮或丁丙诺啡可能会增加日后出现焦虑样行为的风险，但这种影响取决于特定的亚组特征。需要进一步的研究来得出明确的结论。
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