Serotonin Reciprocally Regulates Melanocortin Neurons to Modulate Food Intake

Lora K. Heisler, Erin E. Jobst, Gregory M. Sutton, Ligang Zhou, Erzsebet Borok, Zoe Thornton-Jones, Hong Yan Liu, Jeffrey M. Zigman, Nina Balthasar, Toshiro Kishi, Charlotte E. Lee, Carl J. Aschkenasi, Chen Yu Zhang, Jia Yu, Olivier Boss, Kathleen G. Mountjoy, Peter G. Clifton, Bradford B. Lowell, Jeffrey M. Friedman, Tamas HorvathAndrew A. Butler, Joel K. Elmquist, Michael A. Cowley

Research output: Contribution to journalArticlepeer-review

318 Scopus citations


The neural pathways through which central serotonergic systems regulate food intake and body weight remain to be fully elucidated. We report that serotonin, via action at serotonin1B receptors (5-HT1BRs), modulates the endogenous release of both agonists and antagonists of the melanocortin receptors, which are a core component of the central circuitry controlling body weight homeostasis. We also show that serotonin-induced hypophagia requires downstream activation of melanocortin 4, but not melanocortin 3, receptors. These results identify a primary mechanism underlying the serotonergic regulation of energy balance and provide an example of a centrally derived signal that reciprocally regulates melanocortin receptor agonists and antagonists in a similar manner to peripheral adiposity signals.

Original languageEnglish (US)
Pages (from-to)239-249
Number of pages11
Issue number2
StatePublished - Jul 20 2006



ASJC Scopus subject areas

  • Neuroscience(all)


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