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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.

Original publication

DOI

10.1016/j.tips.2007.10.009

Type

Journal article

Journal

Trends Pharmacol Sci

Publication Date

12/2007

Volume

28

Pages

629 - 636

Keywords

Animals, Autoreceptors, Feedback, Physiological, Humans, Receptor, Serotonin, 5-HT1A, Receptors, Serotonin, 5-HT2, Serotonin, Serotonin Antagonists, gamma-Aminobutyric Acid