Antidepressant and anxiolytic effects of selective 5-HT6 receptor agonists in rats.
Antidepressant and anxiolytic effects of selective 5-HT6 receptor agonists in rats.
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DOI：
10.1007/s00213-010-1798-7
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发表时间：
2011-02
影响因子：
3.4
通讯作者：
Lucki, Irwin
中科院分区：
文献类型：
--
作者：
Carr, Gregory V.;Schechter, Lee E.;Lucki, Irwin
关键词：
虽然选择性5-羟色胺再摄取抑制剂（SSRIs）通过增强多巴胺能神经传递对抑郁症和焦虑症产生临床治疗作用，但对5-HT 6受体在治疗心境障碍中的潜在作用知之甚少。本研究的目的是使用已建立的大鼠行为测试来测试5-HT 6受体激动剂WAY-208466和WAY-181187的潜在抗抑郁样和抗焦虑样作用。为了确定5-HT 6受体激动剂是否具有抗抑郁样活性，用WAY-208466或WAY-181187处理大鼠，并在改良的大鼠强迫游泳试验（FST）中进行测试。此外，使用防御性埋藏（DB）试验和新奇诱导的摄食量减少（NIH）试验测量了WAY-208466和WAY-181187的潜在抗焦虑样作用。WAY-208466和WAY-181187产生抗抑郁样和抗焦虑样作用。这两种化合物降低不动性和增加游泳行为的FST。5-HT 6受体激动剂的作用与SSRI氟西汀治疗后观察到的作用相似。两种5-HT 6受体激动剂在DB试验中也减少了埋藏持续时间，表明试验中的抗焦虑活性。在NIH试验中重现了WAY-208466的抗焦虑作用。NIH中WAY-181187的抗焦虑作用评估受到笼舍喂养行为改变的混淆。这些研究结果表明，5-HT 6受体激动剂可能代表一类新的潜在抗抑郁药和抗焦虑药化合物，并可能拥有许多优势，目前可用的治疗，包括快速起效的抗焦虑疗效。
Although selective serotonin reuptake inhibitors (SSRIs) produce clinical therapeutic effects on depression and anxiety through augmentation of serotonergic neurotransmission, there is little known about the potential contributions of the 5-HT6 receptor in the treatment of mood disorders. The aim of this study was to test the potential antidepressant-like and anxiolytic-like effects of the 5-HT6 receptor agonists WAY-208466 and WAY-181187 using established behavioral tests in rats. In order to determine if the 5-HT6 receptor agonists possess antidepressant-like activity, rats were treated with WAY-208466 or WAY-181187 and tested in the modified rat forced swim test (FST). Also, the potential anxiolytic-like effects of WAY-208466 and WAY-181187 were measured using the defensive burying (DB) test and novelty-induced hypophagia (NIH) test. WAY-208466 and WAY-181187 produced both antidepressant-like and anxiolytic-like effects. Both compounds decreased immobility and increased swimming behavior in the FST. The effects of the 5-HT6 receptor agonists were similar to those seen after treatment with the SSRI fluoxetine. Both 5-HT6 receptor agonists also decreased burying duration in the DB test, indicative of anxiolytic activity in the test. The anxiolytic effects of WAY-208466 were reproduced in the NIH test. Assessment of the anxiolytic effects of WAY-181187 in the NIH was confounded by alterations in home cage feeding behavior. These findings suggest that 5-HT6 receptor agonists may represent a new class of potential antidepressant and anxiolytic compounds and could possess a number of advantages over currently available treatments, including rapid onset of anxiolytic efficacy.
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影响因子：
3.4
作者：
Loiseau, Florence;Dekeyne, Anne;Millan, Mark J.
通讯作者：
Millan, Mark J.
影响因子：
3.4
作者：
Burnham, Katherine E.;Baxter, Mark G.;Sharp, Trevor
通讯作者：
Sharp, Trevor
抗抑郁药的药理学
影响因子：
2.9
作者：
Frazer, A
通讯作者：
Frazer, A
DOI：
10.1016/b978-0-12-374634-4.00030-7
发表时间：
2010-01-01
期刊：
HANDBOOK OF BEHAVIORAL NEUROBIOLOGY OF SEROTONIN
影响因子：
--
作者：
Carr, Gregory V.;Lucki, Irwin
通讯作者：
Lucki, Irwin
影响因子：
8.2
作者：
LUCKI, I;SINGH, A;KREISS, DS
通讯作者：
KREISS, DS