Contributions of 5-HT2C receptors to multiple actions of central serotonin systems

Insights into neural mechanisms through which central serotonin (5-HT) systems influence brain function may be gained by examining the contributions of individual 5-HT receptor subtypes. Significant attention has focused on the 5-HT2C receptor subtype, which is abundantly expressed throughout the central nervous system and displays high-affinity interactions with a wide variety of psychiatric medications. Both pharmacological and genetic approaches to the analysis of 5-HT2C receptor function reveal that it contributes substantially to the serotonergic regulation of a wide variety of behavioral and physiological processes. For example, significant inhibitory effects of 5-HT2C receptor stimulation have been observed in both limbic and striatal dopamine pathways, These may contribute to the effects of experimental 5-HT2C receptor manipulations on responses to psychostimulant, atypical antipsychotic and antidepressant drugs. Further evidence for a role of these receptors in affect regulation arises from recent findings that alterations in 5-HT2C in RNA editing are observed in the brains of suicide victims with a history of depression and in animals exposed to antidepressant drug treatment. Finally, we will review a g-rowing body of evidence indicating a role of 5HT(2C) receptors in the serotonergic regulation of energy balance. Pharmacological and genetic studies reveal these receptors to influence feeding, glucose homeostasis and the energy efficiency of physical activity. (C) 2004 Elsevier B.V. All rights reserved.