Effects of repeated fluoxetine on anxiety-related behaviours, central serotonergic systems, and the corticotropic axis in SHR and WKY rats
Effects of repeated fluoxetine on anxiety-related behaviours, central serotonergic systems, and the corticotropic axis in SHR and WKY rats
复制标题
重复服用氟西汀对 SHR 和 WKY 大鼠焦虑相关行为、中枢血清素能系统和促肾上腺皮质激素轴的影响
DOI：
10.1016/s0028-3908(99)00009-x
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发表时间：
1999-06-01
影响因子：
4.7
通讯作者：
Chaouloff, F
中科院分区：
文献类型：
--
作者：
Durand, M;Berton, O;Chaouloff, F
为了与选择性5-羟色胺再摄取抑制剂（SSRI）在人体中的抗焦虑特性保持一致，我们在自发性高血压大鼠（SHR）和Wistar-Kyoto（WKY）大鼠（分别表现出低焦虑和高焦虑）中研究了SSRI氟西汀重复治疗（5或10 mg/kg，每日，持续3周）的一些精神神经内分泌效应。最后一次注射后两天，氟西汀的血浆水平未检测到，而其代谢产物去甲氟西汀的血浆水平在两种菌株中均以相似的程度存在。通过高架十字迷宫试验（氟西汀第13次给药后29-30 h）和旷场试验（氟西汀末次注射后48 h），观察到氟西汀预处理未产生抗焦虑作用;因此，通过主成分分析和急性地西泮研究评估，部分（但非全部）行为提示焦虑和运动不足。在这两种品系中，10 mg/kg剂量的氟西汀降低了下丘脑5-HT和5-HIAA水平，并降低了中脑和/或海马5-HT转运体上的[（3）H]西酞普兰结合，但不影响海马5-HT（1A）受体上的[（3）H]8-羟基2-（二-N-丙基氨基）四氢萘结合。然而，氟西汀引起的海马5-HT转运蛋白结合的减少在WKY大鼠中比在SHR大鼠中重要得多，这种应变依赖性效应在WKY大鼠中与皮质[（3）H]酮色林在5-HT（2A）受体上结合的减少有关。最后，在WKY大鼠中，重复给予氟西汀增加肾上腺重量和血浆皮质酮对旷场暴露的反应，但不影响海马盐皮质激素和糖皮质激素受体的结合能力。这些数据表明，重复氟西汀给药的关键精神神经内分泌反应可能是紧张依赖性的，重复氟西汀给药不会产生抗焦虑作用，如两个标准的情绪测试所评估的。(C)1999 Elsevier Science Ltd.保留所有权利。
In keeping with the anxiolytic property of selective serotonin reuptake inhibitors (SSRIs) in humans, we have examined in the spontaneously hypertensive rat (SHR) and the Wistar-Kyoto (WKY) rat, which display low and high anxiety, respectively, some psychoneuroendocrine effects of a repeated treatment with the SSRI fluoxetine (5 or 10 mg/kg daily, for 3 weeks). Two days after the last injection, plasma levels of fluoxetine were not detectable whereas those of its metabolite, norfluoxetine, were present to similar extents in both strains. By means of the elevated plus-maze test (29-30 h after the 13th administration of fluoxetine) and an open field test (48 h after the last injection of fluoxetine), it was observed that fluoxetine pretreatment did not yield anxiolysis; hence, some, but not all, behaviours were indicative of anxiety and hypolocomotion las assessed through principal component analyses and acute diazepam studies). In both strains, the 10 mg/kg dose of fluoxetine decreased hypothalamus 5-HT and 5-HIAA levels, and reduced midbrain and/or hippocampus [(3)H]citalopram binding at 5-HT transporters, but did not affect [(3)H]8-hydroxy2-(di-N-propylamino)tetralin binding at hippocampal 5-HT(1A) receptors. However, the fluoxetine-elicited reduction in hippocampal 5-HT transporter binding was much more important in WKY than in SHR rats, this strain-dependent effect being associated in WKY rats with a reduction in cortical [(3)H]ketanserin binding at 5-HT(2A) receptors. Lastly, in WKY rats, repeated fluoxetine administration increased adrenal weights and the plasma corticosterone response to open field exposure, but did not affect the binding capacities of hippocampal mineralocorticoid and glucocorticoid receptors. These data show that key psychoneuroendocrine responses to repeated fluoxetine administration may be strain-dependent, and that repeated fluoxetine administration does not yield anxiolysis, as assessed by two standard tests of emotivity. (C) 1999 Elsevier Science Ltd. All rights reserved.