CENTRAL SEROTONERGIC PATHWAYS REGULATING ENERGY BALANCE

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Elucidating the basic neurobiology of energy homeostasis is paramount in the prevention of obesity and type II diabetes. Recently, substantial support for the central melanocortin pathways, through the melanocortin-4 receptors (MC4-Rs), in the regulation of metabolic, neuroendocrine, and behavioral parameters of energy balance has been reported in human and animal studies. However, relatively little is known about CNS MC4-R expression and pathways modulating these physiological and behavioral effects. The neurotransmitter serotonin (5-hydroxytryptamine, 5-HT) is ideally positioned to contribute to the actions of central MC4-R, based on projection pathways and receptor expression. We have strong preliminary data indicating that brain 5-HT pathways regulate melanocortin neurons. The research outlined in this proposal will investigate the role of 5-HT and specific 5-HT receptors in the modulation of the CNS melanocortin system in physiological and behavioral processes associated with obesity and type II diabetes. We offer a seies of neuroanatomical, pharmacological, genetic, physiological, behavioral and electrophysiological experiments to test components of this model. We anticipate that the studies outlined in this proposal will contribute to a better understanding of the complex neural circuitry regulating obesity and type II diabetes and may provide new directions for treatment.