Adolescent fluoxetine treatment mediates a persistent anxiety-like outcome in female C57BL/6 mice that is ameliorated by fluoxetine re-exposure in adulthood.
Adolescent fluoxetine treatment mediates a persistent anxiety-like outcome in female C57BL/6 mice that is ameliorated by fluoxetine re-exposure in adulthood.
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DOI：
10.1038/s41598-021-87378-6
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发表时间：
2021-04-08
影响因子：
4.6
通讯作者：
Iñiguez SD
中科院分区：
文献类型：
--
作者：
Flores-Ramirez FJ;Themann A;Sierra-Fonseca JA;Garcia-Carachure I;Castillo SA;Rodriguez M;Lira O;Preciado-Piña J;Warren BL;Robison AJ;Iñiguez SD
本研究的目的是评估青少年氟西汀（FLX）暴露是否会诱导对焦虑诱导环境的基线反应的长期变化，如果是，成年后再次暴露是否会改善这种焦虑样表型。另一个目的是评估青少年FLX预处理及其在成年后再次暴露对海马和前额叶皮质内5-羟色胺转运蛋白（5-HTT）和脑源性神经营养因子（BDNF）相关信号标志物（TrkB-ERK 1/2-CREB-proBDNF-mBDNF）的影响。为此，雌性C57 BL/6小鼠在产后（PD）35-49天期间暴露于饮用水中的FLX。在21天洗脱期（PD 70）后，对小鼠实施安乐死（组织收集）或进行焦虑相关试验（旷场、明/暗箱、高架十字迷宫）评价。幼年FLX病史导致持续的回避样特征，沿着BDNF信号标志物的减少，但在两个脑区中的5-HTTs或TrkB受体没有减少。有趣的是，在成年期再次暴露于FLX逆转了所有行为任务中持久的FLX诱导的焦虑相关反应，同时将ERK 2-CREB-proBDNF标记物恢复到对照水平，并增加了前额叶皮层中的mBDNF，但不是海马。总的来说，这些结果表明，青少年FLX的历史介导的神经行为适应，持续到成年，这是一个广义的焦虑样表型的指示，这种持续的影响是改善晚年的FLX再曝光，在前额叶皮层特定的方式。
The objective of this study was to evaluate whether juvenile fluoxetine (FLX) exposure induces long-term changes in baseline responses to anxiety-inducing environments, and if so, whether its re-exposure in adulthood would ameliorate this anxiety-like phenotype. An additional goal was to assess the impact of adolescent FLX pretreatment, and its re-exposure in adulthood, on serotonin transporters (5-HTT) and brain-derived-neurotrophic-factor (BDNF)-related signaling markers (TrkB-ERK1/2-CREB-proBDNF-mBDNF) within the hippocampus and prefrontal cortex. To do this, female C57BL/6 mice were exposed to FLX in drinking water during postnatal-days (PD) 35–49. After a 21-day washout-period (PD70), mice were either euthanized (tissue collection) or evaluated on anxiety-related tests (open field, light/dark box, elevated plus-maze). Juvenile FLX history resulted in a persistent avoidance-like profile, along with decreases in BDNF-signaling markers, but not 5-HTTs or TrkB receptors, within both brain regions. Interestingly, FLX re-exposure in adulthood reversed the enduring FLX-induced anxiety-related responses across all behavioral tasks, while restoring ERK2-CREB-proBDNF markers to control levels and increasing mBDNF within the prefrontal cortex, but not the hippocampus. Collectively, these results indicate that adolescent FLX history mediates neurobehavioral adaptations that endure into adulthood, which are indicative of a generalized anxiety-like phenotype, and that this persistent effect is ameliorated by later-life FLX re-exposure, in a prefrontal cortex-specific manner.
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影响因子：
1.7
作者：
Beesdo, Katja;Knappe, Susanne;Pine, Daniel S.
通讯作者：
Pine, Daniel S.
影响因子：
6.6
作者：
Flores-Ramirez, Francisco J.;Parise, Lyonna F.;Iniguez, Sergio D.
通讯作者：
Iniguez, Sergio D.
DOI：
10.1073/pnas.172091899
发表时间：
2002-08-20
影响因子：
11.1
作者：
Barrot, M;Olivier, JDA;Nestler, EJ
通讯作者：
Nestler, EJ
影响因子：
3.5
作者：
Anderson, GD
通讯作者：
Anderson, GD
DOI：
10.1177/0706743719830024
发表时间：
2019-04-01
影响因子：
4
作者：
Georgiades, Katholiki;Duncan, Laura;Wekerle, Christine
通讯作者：
Wekerle, Christine