Contributions of 5-HT(2C) 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-HT(2C) 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-HT(2C) 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-HT(2C) receptor stimulation have been observed in both limbic and striatal dopamine pathways. These may contribute to the effects of experimental 5-HT(2C) 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-HT(2C) mRNA 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 growing body of evidence indicating a role of 5-HT(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.