Bursts and the Efficacy of Selective Serotonin Reuptake Inhibitors
Bursts and the Efficacy of Selective Serotonin Reuptake Inhibitors
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DOI：
10.1055/s-0031-1273697
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发表时间：
2011-05-01
影响因子：
4.3
通讯作者：
Reed, M.
中科院分区：
文献类型：
--
作者：
Best, J.;Nijhout, H. F.;Reed, M.
我们提出了关于选择性血清素再摄取抑制剂（SSRI）功效的新假设。我们认为，尽管平均细胞外 5HT 浓度仍然较低，SSRI 仍可使中缝核细胞的阶段性放电反应恢复正常。我们讨论中缝核中的爆发放电，并使用数学模型来论证强直放电和相位放电可能是解耦的，并且可能来自不同的机制。我们使用末端血清素合成、释放和再摄取的数学模型来说明正常个体和囊泡血清素水平低的个体末端区域对爆发的反应。然后我们证明，急性剂量的 SSRI 不会使爆发反应恢复正常，但长期剂量确实会使反应恢复正常。这些模型结果需要通过新的电生理学和药理学实验来证实。
We present a new hypothesis for the efficacy of selective serotonin reuptake inhibitors (SSRIs). We propose that SSRIs bring the response to the phasic firing of raphe nucleus cells back to normal, even though the average extracellular 5HT concentration remains low. We discuss burst firing in the raphe nuclei and use mathematical models to argue that tonic firing and phasic firing may be decoupled and may come from different mechanisms. We use a mathematical model for serotonin synthesis, release, and reuptake in terminals to illustrate the responses in terminal regions to bursts in a normal individual and in an individual with low vesicular serotonin. We then show that acute doses of SSRIs do not bring the response to bursts back to normal, but that chronic doses do return the response to normal. These model results need to be confirmed by new electrophysiological and pharmacological experiments.