Important messages in the 'post': recent discoveries in 5-HT neurone feedback control.
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.
Sharp
Trevor
T
University Department of Pharmacology, Mansfield Road, Oxford, UK. trevor.sharp@pharm.ox.ac.uk
Boothman
Laura
L
Raley
Josie
J
Quérée
Philip
P
D000818:Animals; D017660:Autoreceptors / Q000502:physiology; D025461:Feedback, Physiological / Q000502:physiology*; D006801:Humans; D044282:Receptor, Serotonin, 5-HT1A / Q000502:physiology*; D044348:Receptors, Serotonin, 5-HT2 / Q000502:physiology*; D012701:Serotonin / Q000502:physiology*; D012702:Serotonin Antagonists / Q000627:therapeutic use; D005680:gamma-Aminobutyric Acid / Q000502:physiology
D017660:Autoreceptors; D044348:Receptors, Serotonin, 5-HT2; D012702:Serotonin Antagonists; D044282:Receptor, Serotonin, 5-HT1A; D012701:Serotonin; D005680:gamma-Aminobutyric Acid