Acute selective serotonin Reuptake inhibitors increase conditioned fear expression:: Blockade with a 5-HT2C receptor antagonist
Acute selective serotonin Reuptake inhibitors increase conditioned fear expression:: Blockade with a 5-HT2C receptor antagonist
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DOI：
10.1016/j.biopsych.2006.11.023
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发表时间：
2007-11-15
影响因子：
10.6
通讯作者：
LeDoux, Joseph E.
中科院分区：
文献类型：
--
作者：
Burghardt, Nesha S.;Bush, David E. A.;LeDoux, Joseph E.
背景：选择性血清素再摄取抑制剂（SSRI）可有效治疗各种焦虑症，尽管焦虑症状在治疗早期往往会加剧。我们之前报道过，用 SSRI 西酞普兰进行急性治疗可增强听觉恐惧调节的获得，这与临床报道的最初致焦虑作用一致。在这里，我们通过评估急性 SSRI 治疗对先前获得性条件性恐惧表达的影响来扩展我们的发现。方法：大鼠在不使用药物的情况下接受恐惧条件性恐惧。第二天在药物治疗后测试了音调诱发的恐惧反应。该方案比预处理治疗更接近临床环境，因为它评估治疗对预先存在的恐惧的影响，而不是对新恐惧记忆形成的影响。 结果：单次预测试注射 SSRls 西酞普兰或氟西汀显着增加恐惧表达。抗抑郁药噻奈普汀或去甲肾上腺素再摄取抑制剂托莫西汀没有作用，表明这种作用是SSR1所特有的。 5-HT3受体拮抗剂托烷司琼不能阻断SSRI诱导的恐惧表达增强，但可以被特异性5-HT2C受体拮抗剂SB 242084阻断。结论：5-HT2C受体激活增强可能是治疗期间最初观察到的SSR1产生焦虑作用的机制。
Background: Selective serotonin reuptake inhibitors (SSRIs) effectively treat various anxiety disorders, although symptoms of anxiety are often exacerbated during early stages of treatment. We previously reported that acute treatment with the SSRI citalopram enhances the acquisition of auditory fear conditioning, which is consistent with the initial anxiogenic effects reported clinically. Here, we extend our findings by assessing the effects of acute SSRI treatment on the expression of previously acquired conditioned fear.Methods: Rats underwent fear conditioning drug-free. Tone-evoked fear responses were tested after drug treatment the following day. This protocol more closely resembles the clinical setting than pre-conditioning treatment, because it evaluates effects of treatment on a pre-existing fear rather than on the formation of a new fear memory.Results: A single pre-testing injection of the SSRls citalopram or fluoxetine significantly increased fear expression. There was no effect of the antidepressant tianeptine or the norepinephrine reuptake inhibitor tomoxetine, indicating that this effect is specific to SSRls. The SSRI-induced enhancement in fear expression was not blocked by tropisetron, a 5-HT3 receptor antagonist, but was blocked by SB 242084, a specific 5-HT2C receptor antagonist.Conclusions: Enhanced activation of 5-HT2C receptors might be a mechanism for the anxiogenic effects of SSRls observed initially during treatment.