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Perinatal fluoxetine treatment promotes long-term behavioral changes in adult mice.
Metabolic Brain Disease ( IF 3.2 ) Pub Date : 2020-08-22 , DOI: 10.1007/s11011-020-00606-2
Roberto Laureano-Melo 1, 2 , Raoni Conceição Dos-Santos 1 , Rodrigo Rodrigues da Conceição 3 , Janaina Sena de Souza 3 , Raphael da Silva Lau 1 , Samantha da Silva Souza Silva 1 , Bruno Guimarães Marinho 1 , Gisele Giannocco 3 , R G Ahmed 4 , Wellington da Silva Côrtes 1
Affiliation  

Serotonin exerts a significant role in the mammalian central nervous system embryogenesis and brain ontogeny. Therefore, we investigate the effect of perinatal fluoxetine (FLX), a selective serotonin reuptake inhibitor, administration on the behavioral expression of adult male Swiss mice. For this purpose, two groups (n = 6 each, and ~ 35 g) of pregnant female Swiss mice were mated. Their offspring were treated with FLX (10 mg/Kg, s.c.) from postnatal day (PND) 5 to 15. At PND 16, one male puppy of each litter was euthanized, and the hippocampus was dissected for RNA analysis. At 70 days of life, the male offspring underwent a behavioral assessment in the open field, object recognition task, light-dark box, tail suspension and rotarod test. According to our results, the programmed animals had a decrease in TPH2, 5HT1a, SERT, BDNF, and LMX1B expression. Also, it was observed less time of immobility in tail suspension test and higher grooming time in the open field test. In the light-dark box test, the FLX-treated offspring had less time in the light side than control. We also observed a low cognitive performance in the object recognition task and poor motor skill learning in the rotarod test. These findings suggest that programming with FLX during the neonatal period alters a hippocampal serotonergic system, promoting anxiety and antidepressant behavior in adults, as well as a low mnemonic capacity.



中文翻译:

围产期氟西汀治疗促进成年小鼠的长期行为改变。

血清素在哺乳动物中枢神经系统胚胎发生和脑个体发育中发挥重要作用。因此,我们研究了围产期氟西汀 (FLX)(一种选择性血清素再摄取抑制剂)对成年雄性瑞士小鼠行为表达的影响。为此,两组(n = 每只 = 6 只,约 35 g) 的怀孕雌性瑞士小鼠交配。他们的后代从出生后第 5 天到第 15 天用 FLX(10 毫克/公斤,皮下)治疗。在 PND 16 日,每窝一只雄性小狗被安乐死,并解剖海马用于 RNA 分析。在 70 天时,雄性后代接受了野外行为评估、物体识别任务、明暗盒、悬尾和旋转棒测试。根据我们的结果,程序化动物的 TPH2、5HT1a、SERT、BDNF 和 LMX1B 表达降低。此外,在悬尾试验中观察到较少的不动时间和在露天试验中较长的梳理时间。在明暗盒测试中,经过 FLX 处理的后代在亮侧的时间少于对照组。我们还观察到物体识别任务中的认知能力低下,旋转杆测试中的运动技能学习能力差。这些发现表明,在新生儿期用 FLX 编程会改变海马血清素系统,促进成人的焦虑和抗抑郁行为,以及低记忆能力。

更新日期:2020-08-22
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