Chronic fluoxetine treatment of juvenile zebrafish (Danio rerio) does not elicit changes in basal cortisol levels and anxiety-like behavior in adulthood
Chronic fluoxetine treatment of juvenile zebrafish (Danio rerio) does not elicit changes in basal cortisol levels and anxiety-like behavior in adulthood
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DOI：
10.7717/peerj.6407
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发表时间：
2019-03-08
期刊：
影响因子：
2.7
通讯作者：
Petrunich-Rutherford, Maureen L.
中科院分区：
文献类型：
--
作者：
Petrunich-Rutherford, Maureen L.
在发育过程中暴露于选择性5 -羟色胺再摄取抑制剂（SSRIs）可能会引起长期的神经适应性变化，从而改变生命后期与压力相关的生理和行为过程的基础调节。目前，在啮齿动物模型中，幼年氟西汀暴露的影响似乎取决于目标发育窗口以及药物暴露的持续时间。斑马鱼（Danio rerio）模型正迅速成为药理学研究的有用工具，可用于帮助阐明性成熟前氟西汀暴露对神经内分泌和行为应激标志物的一些长期影响。在本研究中，斑马鱼幼鱼长期暴露于盐酸氟西汀（0或100 μ g/L） 14天（受精后31-44天（dpf）），然后不进行治疗，直到成年。从90 dpf开始，评估斑马鱼的基础神经内分泌应激和行为反应。从年轻成年斑马鱼体（躯干）中提取皮质醇，并通过酶联免疫吸附试验（ELISA）定量。焦虑样行为被评估为对新水箱测试的反应。在新水箱试验中，预期青少年暴露于氟西汀会(1)降低基础皮质醇水平，(2)在成年期引起抗焦虑作用。然而，在幼年期接触氟西汀与皮质醇基础水平的改变无关，也与年轻成年斑马鱼的焦虑样行为没有任何显著变化。因此，在斑马鱼中，幼年时期的SSRI暴露似乎不会对成年期皮质醇的基础表达和焦虑样行为产生长期不利或不适应的影响。需要进一步的研究来确定在这个发育窗口期暴露SSRI是否会影响神经内分泌和对急性应激的行为反应。
Exposure to selective serotonin reuptake inhibitors (SSRIs) during development may elicit long-term neuroadaptive changes that could alter the basal regulation of stress-associated physiological and behavioral processes later in life. Currently, the effects of juvenile fluoxetine exposure in rodent models appear to be dependent on the developmental window targeted as well as the duration of drug exposure. The zebrafish (Danio rerio) model is rapidly becoming a useful tool in pharmacological research and can be used to help elucidate some of the long-term effects of fluoxetine exposure prior to sexual maturation on neuroendocrine and behavioral stress markers. In the current study, juvenile zebrafish were chronically exposed to fluoxetine hydrochloride (0 or 100 mu g/L) for 14 days (31-44 days post-fertilization (dpf)), then were left untreated until young adulthood. Starting at 90 dpf, basal neuroendocrine stress and behavioral responses of zebrafish were assessed. Cortisol was extracted from the young adult zebrafish body (trunk) and quantified via enzyme-linked immunosorbent assay (ELISA). Anxiety-like behaviors were assessed in response to introduction to the novel tank test. It was expected that juvenile exposure to fluoxetine would (1) reduce basal cortisol levels and (2) elicit anxiolytic effects in the novel tank test in adulthood. However, fluoxetine exposure during the juvenile period was not associated with alterations in basal levels of cortisol nor were there any significant changes in anxiety-like behavior in the young adult zebrafish. Thus, in zebrafish, it does not appear that SSRI exposure during the juvenile period has a long-term adverse or maladaptive impact on the basal expression of cortisol and anxiety-like behavior in adulthood. Further studies are needed to determine if SSRI exposure during this developmental window influences neuroendocrine and behavioral responses to acute stress.