Donders Institute for Brain, Cognition, and Behaviour, Centre for Neuroscience, Department of Cognitive Neuroscience, Radboud University Nijmegen Medical Centre, Geert Grooteplein 21 (route 126), 6525, EZ, Nijmegen, The Netherlands.
Psychopharmacology (Berl). 2011 Oct;217(3):419-32. doi: 10.1007/s00213-011-2299-z. Epub 2011 Apr 14.
Fluoxetine (Prozac®) is the most frequently prescribed drug to battle depression in pregnant women, but its safety in the unborn child has not yet been established. Fluoxetine, a selective serotonin reuptake inhibitor, crosses the placenta, leading to increased extracellular serotonin levels and potentially neurodevelopmental changes in the fetus.
The purpose of this study was to elucidate the long-term consequences of prenatal fluoxetine in rats.
Pregnant rats were injected daily with 12 mg/kg fluoxetine or vehicle from gestational day 11 until birth, and the behavior of the offspring was monitored.
Plasma fluoxetine transfer from mother to pup was 83%, and high levels of fluoxetine (13.0 μg/g) were detected in the pup brain 5 h after the last injection. Fluoxetine-treated dams gave birth to litters 15% smaller than usual and to pups of reduced weight (until postnatal day 7). Furthermore, prenatal fluoxetine exposure significantly increased anxiety in the novelty-suppressed feeding test, the footshock-induced conditioned place aversion test, and the elevated plus maze test (following footshock pre-exposure) during adulthood, and also significantly decreased components of social play behavior at 4 weeks of age, and a strong tendency for increased self-grooming and making less contact in adults. Behavioral despair, anhedonia, and sexual behavior were not different between treatment groups. Finally, the hypothermic response to the 5-HT(1A) agonist flesinoxan was observed at a lower dose in prenatally fluoxetine-exposed rats than in controls.
Prenatal fluoxetine exposure in rats leads to detrimental behavioral outcomes in later life, which may partly be due to altered 5-HT(1A) receptor signaling.
氟西汀（百忧解）是治疗孕妇抑郁症最常开的药物，但它在胎儿中的安全性尚未确定。氟西汀是一种选择性 5-羟色胺再摄取抑制剂，可穿过胎盘，导致细胞外 5-羟色胺水平升高，并可能导致胎儿神经发育改变。
本研究旨在阐明产前氟西汀对大鼠的长期影响。
妊娠第 11 天至分娩，每天给怀孕的大鼠注射 12mg/kg 的氟西汀或载体，监测后代的行为。
母体向幼仔转移的氟西汀血浆浓度为 83%，最后一次注射后 5 小时，幼仔大脑中检测到的氟西汀水平（13.0μg/g）很高。氟西汀处理的母鼠所产的幼仔比正常情况小 15%，体重减轻（直到出生后第 7 天）。此外，产前氟西汀暴露显著增加了成年期新奇抑制喂养试验、足底电击引起的条件性位置厌恶试验和高架十字迷宫试验（足底电击预暴露后）中的焦虑，还显著降低了 4 周龄时的社会玩耍行为成分，并使成年期的自我梳理增加，接触减少。处理组之间的行为绝望、快感缺失和性行为没有差异。最后，与对照组相比，在产前氟西汀暴露的大鼠中，5-HT1A 激动剂 flesinoxan 的体温降低反应出现在较低剂量。
在大鼠中，产前氟西汀暴露会导致后期生活中的不良行为结果，这可能部分是由于 5-HT1A 受体信号改变所致。
