Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

This chapter discusses current knowledge of the pharmacology and physiology of the feedback mechanisms that control serotonin (5-hydroxytryptamine; 5-HT) neurons, and considers their possible contribution to the pathophysiology and treatment of psychiatric disorders, especially major depression. A key mechanism involved in the control of 5-HT neurons is feedback inhibition by presynaptic 5-HT autoreceptors. These autoreceptors are implicated in depression and anxiety neurobiology, and form the basis of various ongoing 5-HT drug discovery efforts in these therapeutic areas. Recent experiments have discovered further complexity of 5-HT neuron control, specifically in the form of postsynaptic feedback mechanisms. These mechanisms have the physiological effects of 5-HT autoreceptors but use additional 5-HT receptor subtypes, and operate via neural inputs to 5-HT neurons. There is also recent evidence for postsynaptic feedback systems that excite 5-HT neurons. The postsynaptic feedback mechanisms are also providing a new source of drug targets for therapeutic application. Overall, current data suggest the presence of a previously unsuspected, complex arrangement of pre- and postsynaptic 5-HT receptor-mediated feedback mechanisms that control 5-HT neuron function. © 2010 Elsevier B.V.

Original publication




Journal article


Handbook of Behavioral Neuroscience

Publication Date





233 - 247