Domingues Rafael R, Wiltbank Milo C, Hernandez Laura L, Adcock Sarah J J
Department of Animal and Dairy Sciences, University of Wisconsin, Madison, WI, USA.
Endocrinology and Reproductive Physiology Program, University of Wisconsin, Madison, WI, USA.
Pediatr Res. 2025 Jan 14. doi: 10.1038/s41390-025-03799-3.
Fluoxetine is commonly prescribed to treat depression during pregnancy. We aimed to evaluate the effects of prenatal fluoxetine exposure on maternal-offspring behavior in a non-depressed sheep model.
On day 119 ± 1 of a 151-day expected gestation, Hampshire ewes were randomly assigned to receive intravenous fluoxetine (10 mg/kg for the first 2 days and 5 mg/kg daily thereafter until parturition) or a control vehicle. Video was recorded of 8 fluoxetine-treated ewes and 10 control ewes for 2 h before and after parturition.
Fluoxetine did not alter dam behavior during the peripartum period, including time spent lying before the first birth, lying bout duration, probability of needing birth assistance, duration of birth assistance when provided, and time spent touching her lambs. However, in utero exposure impaired neonatal vigor as lambs spent less time standing and tended to spend less time nursing compared to unexposed lambs.
Neonatal behavioral impairments are consistent with those associated with fluoxetine exposure during human gestation. This effect appears to be independent of maternal behavior, which was unaffected by antidepressant use.
Lambs exposed to SSRI in utero spent less time standing and tended to spend less time nursing than control lambs, consistent with neonatal behavioral outcomes encountered in clinical practice. The reduced neonatal vigor was likely unrelated to maternal behavior, which was not altered by SSRI treatment. Non-depressed sheep models can help to elucidate the behavioral effects of antidepressant use during pregnancy to enhance health outcomes and patient care.
氟西汀常用于治疗孕期抑郁症。我们旨在评估在非抑郁绵羊模型中,产前暴露于氟西汀对母羊-后代行为的影响。
在预期妊娠期151天的第119±1天,将汉普郡母羊随机分配接受静脉注射氟西汀(前2天为10mg/kg,此后每天5mg/kg直至分娩)或对照载体。对8只接受氟西汀治疗的母羊和10只对照母羊在分娩前后2小时进行录像。
氟西汀并未改变围产期母羊的行为,包括首次分娩前躺卧的时间、躺卧周期时长、需要分娩协助的概率、提供分娩协助时的时长以及触摸羔羊的时间。然而,与未暴露的羔羊相比,子宫内暴露损害了新生羔羊的活力,因为羔羊站立时间减少,哺乳时间也趋于减少。
新生羔羊的行为损害与人类妊娠期暴露于氟西汀所产生的损害一致。这种影响似乎与母羊行为无关,母羊行为未受抗抑郁药使用的影响。
子宫内暴露于选择性5-羟色胺再摄取抑制剂(SSRI)的羔羊站立时间和哺乳时间均比对照羔羊少,这与临床实践中遇到的新生羔羊行为结果一致。新生羔羊活力降低可能与母羊行为无关,母羊行为未因SSRI治疗而改变。非抑郁绵羊模型有助于阐明孕期使用抗抑郁药的行为影响,以改善健康结局和患者护理。