氟西汀通过视交叉上核神经元放电的相位提前来调节昼夜生物钟。
Fluoxetine modulates the circadian biological clock via phase advances of suprachiasmatic nucleus neuronal firing.
作者信息
Sprouse Jeffrey, Braselton John, Reynolds Linda
机构信息
Department of Neuroscience, Pfizer Global Research & Development, Groton, Connecticut 06340, USA.
出版信息
Biol Psychiatry. 2006 Oct 15;60(8):896-9. doi: 10.1016/j.biopsych.2006.03.003. Epub 2006 May 2.
BACKGROUND
The documented ability of serotonin (5-HT) to directly modulate circadian rhythms prompted interest in a similar role for therapeutic agents that readily enhance 5-HT neurotransmission, namely the selective serotonin reuptake inhibitors (SSRIs).
METHODS
Extracellular recordings of unit firing of suprachiasmatic nucleus (SCN) neurons maintained in slice culture enabled determinations of circadian rhythmicity. Shifts in the peak of activity were determined during the next circadian cycle following drug exposure.
RESULTS
Fluoxetine (10 microm, 60 minutes incubation) produced robust phase advances only in the presence of L-tryptophan (.5 microm), added to maintain serotonergic tone.
CONCLUSIONS
Actions of SSRIs at the level of the circadian biological clock add to the list of pharmacological effects for this drug class and encourage speculation as to their importance clinically.
背景
血清素（5-羟色胺，5-HT）能够直接调节昼夜节律，这一特性引发了人们对于能轻易增强5-HT神经传递的治疗药物（即选择性5-羟色胺再摄取抑制剂，SSRIs）是否具有类似作用的兴趣。
方法
在切片培养中对视交叉上核（SCN）神经元的单位放电进行细胞外记录，以此确定昼夜节律性。在药物暴露后的下一个昼夜周期内，测定活动峰值的变化。
结果
仅在添加L-色氨酸（0.5微摩尔）以维持血清素能张力的情况下，氟西汀（10微摩尔，孵育60分钟）才产生显著的相位提前。
结论
SSRIs在昼夜生物钟水平的作用增加了这类药物的药理学效应清单，并引发了关于其临床重要性的猜测。
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