Acute selective serotonin Reuptake inhibitors increase conditioned fear expression:: Blockade with a 5-HT2C receptor antagonist

被引:143
作者
Burghardt, Nesha S.
Bush, David E. A.
McEwen, Bruce S.
LeDoux, Joseph E.
机构
[1] NYU, Ctr Neurol Sci, WM Keck Fdn Lab Neurobiol, New York, NY USA
[2] Rockefeller Univ, Harold & Margaret Milliken Hatch Lab Neuroendocri, New York, NY 10021 USA
关键词
amygdala; citalopram; fear conditioning; serotonin; 5-HT2C receptor; 5-HT3; receptor;
D O I
10.1016/j.biopsych.2006.11.023
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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.
引用
收藏
页码:1111 / 1118
页数:8
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