Nyberg Henriette, Bogen Inger Lise, Nygaard Egil, Achterberg Marijke, Andersen Jannike Mørch
Department of Forensic Sciences, Section of Forensic Research, Oslo University Hospital, PO Box 4950, Oslo, Norway.
Department of Pharmacy, Faculty of Mathematics and Natural Sciences, University of Oslo, Oslo, Norway.
Psychopharmacology (Berl). 2025 Mar;242(3):663-680. doi: 10.1007/s00213-024-06718-2. Epub 2024 Dec 5.
The prevalence of newborns exposed to medications for opioid use disorder (MOUD), such as methadone or buprenorphine, during pregnancy is increasing. The opioid system plays a crucial role in regulating and shaping social behavior, and children prenatally exposed to opioids face an increased risk of developing behavioral problems. However, the impact of prenatal exposure to MOUD on offspring's social behavior during adolescence and adulthood, as well as potential intergenerational effects, remains largely unexplored.
Our study employed a translationally relevant animal model to investigate how maternal (F0) exposure to MOUD during pregnancy affects social behavior in young and adult rats across the first (F1) and second (F2) generation of offspring.
Female Sprague-Dawley rats were implanted with an osmotic minipump delivering methadone (10 mg/kg/day), buprenorphine (1 mg/kg/day), or sterile water, prior to mating with drug-naïve males. Adult F1 females were mated with treatment-matched F1 males to generate F2 offspring. We assessed social play behavior in juvenile offspring, and social interaction behavior in a three-chamber social interaction test in young adults of the F1 and F2 generations.
Maternal exposure to buprenorphine, but not methadone, during pregnancy reduced social play behavior in both F1 and F2 offspring, expressed by a reduced number of pounces and pins, which are the two most characteristic parameters of social play in rats. Adult social interactions were unaffected by prenatal MOUD exposure across both generations.
Maternal exposure to buprenorphine during pregnancy may have adverse effects on social play behavior across two generations of offspring.
孕期接触用于阿片类物质使用障碍（MOUD）的药物（如美沙酮或丁丙诺啡）的新生儿患病率正在上升。阿片系统在调节和塑造社会行为方面起着关键作用，产前接触阿片类物质的儿童出现行为问题的风险增加。然而，产前接触MOUD对青少年期和成年期后代社会行为的影响以及潜在的代际效应在很大程度上仍未得到探索。
我们的研究采用了一个具有转化相关性的动物模型，以研究孕期母本（F0）接触MOUD如何影响第一代（F1）和第二代（F2）后代的幼鼠和成年大鼠的社会行为。
在与未接触过药物的雄性大鼠交配前，给雌性斯普拉格-道利大鼠植入一个渗透微型泵，分别输送美沙酮（10毫克/千克/天）、丁丙诺啡（1毫克/千克/天）或无菌水。成年F1代雌性大鼠与经治疗匹配的F1代雄性大鼠交配，以产生F2代后代。我们评估了幼年后代的社会玩耍行为，以及F1代和F2代成年大鼠在三室社会互动试验中的社会互动行为。
孕期母本接触丁丙诺啡而非美沙酮，会减少F1代和F2代后代的社会玩耍行为，表现为扑咬和压制次数减少，这是大鼠社会玩耍的两个最具特征性的参数。两代大鼠的成年社会互动均未受产前MOUD暴露的影响。
孕期母本接触丁丙诺啡可能对两代后代的社会玩耍行为产生不利影响。
