选择性 5-HT6 受体激动剂对大鼠的抗抑郁和抗焦虑作用。
Antidepressant and anxiolytic effects of selective 5-HT6 receptor agonists in rats.
机构信息
Department of Psychiatry, University of Pennsylvania, Philadelphia, PA 19104, USA.
出版信息
Psychopharmacology (Berl). 2011 Feb;213(2-3):499-507. doi: 10.1007/s00213-010-1798-7. Epub 2010 Mar 9.
RATIONALE
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-HT(6) receptor in the treatment of mood disorders.
OBJECTIVES
The aim of this study was to test the potential antidepressant-like and anxiolytic-like effects of the 5-HT(6) receptor agonists WAY-208466 and WAY-181187 using established behavioral tests in rats.
METHODS
In order to determine if the 5-HT(6) 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.
RESULTS
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-HT(6) receptor agonists were similar to those seen after treatment with the SSRI fluoxetine. Both 5-HT(6) 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.
CONCLUSIONS
These findings suggest that 5-HT(6) 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.
背景
尽管选择性 5-羟色胺再摄取抑制剂（SSRIs）通过增强 5-羟色胺能神经传递而对抑郁和焦虑产生临床治疗效果，但对于 5-HT6 受体在治疗心境障碍中的潜在作用知之甚少。
目的
本研究旨在使用大鼠的既定行为测试来检验 5-HT6 受体激动剂 WAY-208466 和 WAY-181187 的潜在抗抑郁样和抗焦虑样作用。
方法
为了确定 5-HT6 受体激动剂是否具有抗抑郁样活性，将大鼠用 WAY-208466 或 WAY-181187 处理，并在改良的大鼠强迫游泳试验（FST）中进行测试。此外，还使用防御性掩埋（DB）测试和新奇诱导的摄食量减少（NIH）测试来测量 WAY-208466 和 WAY-181187 的潜在抗焦虑样作用。
结果
WAY-208466 和 WAY-181187 均产生抗抑郁样和抗焦虑样作用。这两种化合物均减少 FST 中的不动性并增加游泳行为。5-HT6 受体激动剂的作用与 SSRI 氟西汀治疗后的作用相似。两种 5-HT6 受体激动剂还减少了 DB 测试中的掩埋持续时间，表明该测试中具有抗焦虑活性。WAY-208466 的抗焦虑作用在 NIH 测试中重现。WAY-181187 在 NIH 中的抗焦虑作用评估受到其对笼内进食行为改变的影响。
结论
这些发现表明，5-HT6 受体激动剂可能代表一类新的潜在抗抑郁和抗焦虑化合物，并且与目前可用的治疗方法相比，可能具有许多优势，包括抗焦虑疗效的快速起效。
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