Fluvoxamine increased glutamate release by activating both 5-HT₃ and sigma-1 receptors in prelimbic cortex of chronic restraint stress C57BL/6 mice

详细信息	查看全文 | 推荐本文 |

• 作者：Yingmei Fu^a ; Shunying Yu^a ; Xiaoyun Guo^a ; Xia Li^a ; Ting Li^a ; Huafang Li^a ; Yi Dong^b ; ^{brainstein@fudan.edu.cn}
• 关键词：Fluvoxamine ; Glutamate release ; Sigma-1 receptors ; 5-HT3 receptors ; Synaptosomes
• 刊名：Biochimica et Biophysica Acta (BBA)/Molecular Cell Research
• 出版年：2012
• 期刊代码：20_01674889
• 类别：bio
• 出版时间：April, 2012
• 卷：1823
• 期：4
• 页码：826-837
• 文件大小：1511 K

摘要

Emerging evidence from therapeutic trials in humans and animal models suggests that in the treatment of depression, antidepressants play a role by targeting the glutamatergic system. Fluvoxamine is one of the widely used SSRIs which has been considered to target monoamine neurotransmitter reuptake mechanisms. However, whether fluvoxamine has an effect on the glutamate release is still unclear. The present experiment studied the effect of fluvoxamine on presynaptic glutamate release in prelimbic cortex, both in control C57BL/6 mice and chronic restraint stress C57BL/6 mice, and further investigated the mechanism underlying this effect by using patch clamp, on-line fluorimetry, pharmacological approaches combined with other techniques. The results showed that fluvoxamine increased the glutamate release in the depression model mice but it had no effect on the glutamate release in the control mice. The mechanism underlying these effects in depression model mice was that, fluvoxamine firstly activated presynaptic 5-HT₃ receptors, which transiently increased the Ca²⁺ concentration. The increase of Ca²⁺ concentration via 5-HT₃ receptors caused the activation of sigma-1 receptors, which were activated by fluvoxamine. The activation of sigma-1 receptors increased the intrasynaptosomal Ca²⁺ concentration significantly through the outflow of endoplasmic reticulum calcium and finally activated PKC. These results suggested that fluvoxamine may have a selective effect and different mechanism based on the condition of animal.