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西酞普兰或瑞波西汀的临床剂量可调节强迫游泳试验中不动时间较高或较低的雌性 Wistar 大鼠的被动和主动行为。

Clinical doses of citalopram or reboxetine differentially modulate passive and active behaviors of female Wistar rats with high or low immobility time in the forced swimming test.

机构信息

Departamento de Neurociencias, Universidad Autónoma de Yucatán, Av. Itzaes # 490, Mérida, Yucatán CP 97000, México.

出版信息

Pharmacol Biochem Behav. 2013 Sep;110:89-97. doi: 10.1016/j.pbb.2013.06.003. Epub 2013 Jun 13.

DOI:10.1016/j.pbb.2013.06.003
PMID:23769836
Abstract

The sensitivity of immobility time (IT) to antidepressant-drugs differs in rats expressing high or low motor activity during the forced swimming test (FST). However, whether this heterogeneity is expressed after the administration of the most selective serotonin and norepinephrine reuptake inhibitors (SSRIs and SNRIs, respectively) is unknown. We compared the influence of either the SSRI citalopram or the SNRI reboxetine with the tricyclic antidepressant amitriptyline on two subgroups of female Wistar rats expressing high IT (HI; at or above the mean value) or low IT (LI; below the mean) during the initial 5 min of the first session of the FST. None of the tested drugs increased motor activity in the open field test. When vehicle was applied to either HI or LI rats, IT increased in the second session of the FST. This increment concurred with a simultaneous climbing time (CT) decrement. When amitriptyline (15 mg/kg) was tested the CT increased for both HI and LI rats. This increment was accompanied by an IT decrement in HI and LI rats. Reboxetine (0.16 or 1 mg/kg) precluded IT and CT changes in both HI and LI rats and produced a swimming time reduction. Citalopram (0.4, 1, and 3 mg/kg) essentially mimicked the influence of reboxetine on the IT and CT in LI rats, as well as in HI rats, but in the latter case only at 3 mg/kg. Yet, at the dose of 10 mg/kg citalopram lacked this effect in both subgroups. No differences were detected when the IT of LI rats was evaluated with citalopram (3 mg/kg) during estrus or diestrus stage. These results show that clinical doses of citalopram produced an antidepressant-like effect selectively in LI rats, while amitriptyline or reboxetine produced this effect in both LI and HI animals.

摘要

在强迫游泳试验(FST)中表现出高或低运动活性的大鼠中,不动时间(IT)对抗抑郁药物的敏感性不同。然而,在给予最具选择性的 5-羟色胺和去甲肾上腺素再摄取抑制剂(SSRIs 和 SNRIs,分别)后,这种异质性是否表达尚不清楚。我们比较了 SSRI 西酞普兰或 SNRI 瑞波西汀与三环类抗抑郁药阿米替林对 FST 第一阶段最初 5 分钟内 IT 较高(HI;等于或高于平均值)或较低(LI;低于平均值)的两组雌性 Wistar 大鼠的影响。测试的药物均未增加旷场试验中的运动活性。当将载体应用于 HI 或 LI 大鼠时,FST 的第二阶段 IT 增加。这种增量与同时的爬梯时间(CT)减少同时发生。当给予阿米替林(15 mg/kg)时,HI 和 LI 大鼠的 CT 均增加。这种增加伴随着 HI 和 LI 大鼠 IT 的减少。Reboxetine(0.16 或 1 mg/kg)可防止 HI 和 LI 大鼠的 IT 和 CT 变化,并减少游泳时间。西酞普兰(0.4、1 和 3 mg/kg)基本上模仿了 reboxetine 对 LI 大鼠和 HI 大鼠 IT 和 CT 的影响,但在后一种情况下仅在 3 mg/kg 时。然而,在 10 mg/kg 的剂量下,西酞普兰在两个亚组中均缺乏这种作用。在发情或发情期阶段评估 LI 大鼠的 IT 时,西酞普兰(3 mg/kg)未检测到差异。这些结果表明,西酞普兰的临床剂量选择性地在 LI 大鼠中产生抗抑郁样作用,而阿米替林或瑞波西汀在 LI 和 HI 动物中均产生这种作用。

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