Anxiety-like effects induced by acute fluoxetine, sertraline or m-CPP treatment are reversed by pretreatment with the 5-HT2C receptor antagonist SB-242084 but not the 5-HT1A receptor antagonist WAY-100635
Anxiety-like effects induced by acute fluoxetine, sertraline or m-CPP treatment are reversed by pretreatment with the 5-HT2C receptor antagonist SB-242084 but not the 5-HT1A receptor antagonist WAY-100635
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DOI：
10.1017/s1461145701002632
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发表时间：
2001-12-01
影响因子：
4.8
通讯作者：
Kantor, S
中科院分区：
文献类型：
--
作者：
Bagdy, G;Graf, M;Kantor, S
在雄性Sprague-Dawley大鼠的社交焦虑实验中，检测了5-HT 1A和5-HT 2C受体在恐惧、SSRI抗抑郁药急性治疗或5-HT受体激动剂m-CPP诱导的焦虑中的可能作用。氟西汀（2.5-10 mg/kg，i. p.），舍曲林（15 mg/kg，i. p.）和m-CPP（0.5- 2.0mg/kg，i.p.）在低光、熟悉的竞技场测试条件下，所有人都具有类似焦虑的特征（与载体相比，总社会互动时间减少，自我修饰增加）。所有这些作用可通过预先给予高亚型选择性5-HT_（2C）受体拮抗剂SB-242084（0.05或0.2 mg/kg，i. p.）未能逆转SSRI诱导的总社会互动时间的减少，而且，它增强了自我修饰反应。SB-242084（0.2 mg/kg）和WAY-100635（0.05和0.2 mg/kg）可逆转SSRI抗抑郁药引起的运动不足。在与恐惧相关的强光、不熟悉的竞技场试验条件下，SB-242084单独与溶剂进行试验，在0.2 mg/kg和更高剂量下引起显著的抗焦虑作用。这些结果表明，由急性给予SSRI抗抑郁药或m-CPP引起的啮齿类动物焦虑增加，可能还有人类焦虑增加（例如SSRI后的激动或神经过敏和m-CPP后的恐慌），是由5-HT 2C 1受体激活介导的。5-HT 1A自身受体的阻断可能加重SSRI抗抑郁药的某些急性不良反应。5-HT 1A和5-HT 2C受体均参与SSRI诱导的自发活动减少。此外，我们的研究证实了亚型选择性5-HT 2C受体拮抗剂具有强抗焦虑作用的数据。
The possible role of 5-HT1A and 5-HT2C receptors in the anxiety induced by fear, acute treatment with SSRI antidepressants or the 5-HT receptor agonist m-CPP were tested in the social interaction anxiety test in male Sprague-Dawley rats. Fluoxetine (2.5-10 mg/kg, i.p.), sertraline (15 mg/kg, i.p.) and m-CPP (0.5-2.0 mg/kg, i.p.) all had an anxiogenic-like profile (decrease in time of total social interaction and increase in self-grooming compared to vehicle) under low-light, familiar arena test conditions. All these effects were reversed by pretreatment with the highly subtype-selective 5-HT2C receptor antagonist, SB-242084 at doses of either 0.05 or 0,2 mg/kg, i.p. In contrast, the selective 5-HT,, receptor antagonist WAY-100635 (0.05 and 0.2 mg/kg, s.c.) failed to reverse SSRI-induced decrease in time of total social interaction, further, it augmented self-grooming response. SB-242084 (0.2 mg/kg) and WAY-100635 (0.05 and 0.2 mg/kg) reversed hypolocomotion caused by the SSRI antidepressants. SB-242084, tested alone against vehicle under high-light, unfamiliar arena test conditions associated with fear, caused significant anxiolysis at 0.2 mg/kg and higher doses. These results suggest that increased anxiety in rodents, and possibly, also in humans (e.g. agitation or jitteriness after SSRIs and panic after m-CPP), caused by acute administration of SSRI antidepressants or m-CPP, are mediated by activation of 5-HT2C, receptors. Blockade of 5-HT1A autoreceptors may exacerbate certain acute adverse effects of SSRI antidepressants, Both 5-HT1A and 5-HT2C receptors are involved in the SSRI-induced decrease in locomotor activity. In addition, our studies confirm data that subtype-selective 5-HT2C receptor antagonists have strong anxiolytic actions.