Sharp Trevor, Boothman Laura, Raley Josie, Quérée Philip
University Department of Pharmacology, Mansfield Road, Oxford, UK.
Trends Pharmacol Sci. 2007 Dec;28(12):629-36. doi: 10.1016/j.tips.2007.10.009. Epub 2007 Nov 9.
The neurotransmitter 5-hydroxytryptamine (5-HT, serotonin) mediates important brain functions and contributes to the pathophysiology and successful drug treatment of many common psychiatric disorders, especially depression. It is established that a key mechanism involved in the control of 5-HT neurones is feedback inhibition by presynaptic 5-HT autoreceptors, which are located on 5-HT cell bodies and nerve terminals. However, recent experiments have discovered an unexpected complexity of 5-HT neurone control, specifically in the form of postsynaptic 5-HT feedback mechanisms. These mechanisms have the physiological effects of 5-HT autoreceptors but use additional 5-HT receptor subtypes and operate through neural inputs to 5-HT neurones. A postsynaptic feedback system that excites 5-HT neurones has also been reported. This article discusses current knowledge of the pharmacology and physiology of these new found 5-HT feedback mechanisms and considers their possible contribution to depression pathophysiology and utility as a resource of novel antidepressant drug strategies.
神经递质5-羟色胺（5-HT，血清素）介导重要的脑功能，并在许多常见精神疾病，尤其是抑郁症的病理生理学和成功药物治疗中发挥作用。已确定，参与5-HT神经元控制的一个关键机制是突触前5-HT自身受体的反馈抑制，这些受体位于5-HT细胞体和神经末梢上。然而，最近的实验发现了5-HT神经元控制存在意想不到的复杂性，特别是以突触后5-HT反馈机制的形式。这些机制具有5-HT自身受体的生理效应，但使用额外的5-HT受体亚型，并通过对5-HT神经元的神经输入起作用。也有报道称存在一种能兴奋5-HT神经元的突触后反馈系统。本文讨论了这些新发现的5-HT反馈机制的药理学和生理学的当前知识，并考虑了它们对抑郁症病理生理学的可能贡献以及作为新型抗抑郁药物策略来源的效用。
