Serotonergic Feedback Control
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.