Long-Term Consequences of Neonatal Fluoxetine Exposure in Adult Rats
Long-Term Consequences of Neonatal Fluoxetine Exposure in Adult Rats
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DOI：
10.1002/dneu.22185
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发表时间：
2014-10-01
影响因子：
3
通讯作者：
Lee, Li-Jen
中科院分区：
文献类型：
--
作者：
Ko, Meng-Ching;Lee, Lukas Jyuhn-Hsiarn;Lee, Li-Jen
5-羟色胺（5-HT）在神经发育过程中起着重要作用。选择性血清素再摄取抑制剂（SSRI）型药物在妊娠期间的管理可能会影响胎儿大脑的成熟和随后的脑功能。为了模拟妊娠晚期SSRI暴露的情况，我们在出生后第一周（大致相当于人类妊娠晚期）给新生大鼠氟西汀（FLX）。暴露于flx的成年雄性大鼠表现出运动活动减少和抑郁样行为。此外，感觉运动门控能力也受损。有趣的是，暴露于flx的大鼠的社交互动增加了。当检测5-羟色胺和色氨酸羟化酶水平时，FLX大鼠与对照组（CON）大鼠相比未发现显著变化。FLX大鼠的行为表型提示边缘系统功能障碍。研究了内侧前额叶皮层（mPFC）和基底外侧杏仁核（BLA）神经元的树突结构。与对照组相比，FLX大鼠的第II/III层mPFC锥体神经元具有丰富的树突分支，末端段延长。在BLA锥体神经元中，两组之间的树突分布具有可比性。然而，在FLX大鼠中，mPFC和BLA的树突棘密度均降低。总之，我们的研究结果表明，早期FLX治疗对成年大鼠的情绪和社会行为有长期影响，在成年大鼠中，边缘系统的神经元结构受损也被注意到。怀孕期间服用ssri类抗抑郁药的风险应予以考虑。(c) 2014 Wiley期刊公司
Serotonin (5-HT) plays important roles during neural development. Administration of selective serotonin reuptake inhibitor (SSRI)-type medication during gestation may influence the maturation of the fetal brain and subsequent brain functions. To mimic the condition of late-gestation SSRI exposure, we administered fluoxetine (FLX) in neonatal rats during the first postnatal week, which roughly corresponds to the third trimester period of human gestation. FLX-exposed adult male rats exhibited reduced locomotor activity and depression-like behaviors. Furthermore, sensorimotor gating capacity was also impaired. Interestingly, increased social interaction was noticed in FLX-exposed rats. When the levels of 5-HT and tryptophan hydroxylase were examined, no significant changes were found in FLX rats compared to control (CON) rats. The behavioral phenotypes of FLX rats suggested malfunction of the limbic system. Dendritic architectures of neurons in the medial prefrontal cortex (mPFC) and basolateral amygdala (BLA) were examined. Layer II/III mPFC pyramidal neurons in FLX rats had exuberant dendritic branches with elongated terminal segments compared to those in CON rats. In BLA pyramidal neurons, the dendritic profiles were comparable between the two groups. However, in FLX rats, the density of dendritic spines was reduced in both mPFC and BLA. Together, our results demonstrated the long-lasting effects of early FLX treatment on emotional and social behaviors in adult rats in which impaired neuronal structure in the limbic system was also noticed. The risk of taking SSRI-type antidepressants during pregnancy should be considered. (c) 2014 Wiley Periodicals, Inc.