The hypothalamic neuropeptide melanin-concentrating hormone acts in the nucleus accumbens to modulate feeding behavior and forced-swim performance

Dan Georgescu, Robert M. Sears, Jonathan D. Hommel, Michel Barrot, Carlos A. Bolaños, Donald J. Marsh, Maria A. Bednarek, James A. Bibb, Eleftheria Maratos-Flier, Eric J. Nestler, Ralph J. DiLeone

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243 Scopus citations

Abstract

Melanin-concentrating hormone (MCH) is a hypothalamic neuropeptide with a prominent role in feeding and energy homeostasis. The rodent MCH receptor (MCH1R) is highly expressed in the nucleus accumbens shell (AcSh), a region that is important in the regulation of appetitive behavior. Here we establish a role for MCH and MCH1R in mediating a hypothalamic-limbic circuit that regulates feeding and related behaviors. Direct delivery of an MCH1R receptor antagonist to the AcSh blocked feeding and produced an antidepressant-like effect in the forced swim test, whereas intra-AcSh injection of MCH had the opposite effect. Expression studies demonstrated that MCH1R is present in both the enkephalin- and dynorphin-positive medium spiny neurons of the AcSh. Biochemical analysis in AcSh explants showed that MCH signaling blocks dopamine-induced phosphorylation of the AMPA glutamate receptor subunit GluR1 at Ser845. Finally, food deprivation, but not other stressors, stimulated cAMP response element-binding protein-dependent pathways selectively in MCH neurons of the hypothalamus, suggesting that these neurons are responsive to a specific set of physiologically relevant conditions. This work identifies a novel hypothalamic-AcSh circuit that influences appetitive behavior and mediates the antidepressant activity of MCH1R antagonists.

Original languageEnglish (US)
Pages (from-to)2933-2940
Number of pages8
JournalJournal of Neuroscience
Volume25
Issue number11
DOIs
Publication statusPublished - Mar 16 2005

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Keywords

  • Accumbens
  • Appetite
  • Depression
  • Feeding
  • Lateral hypothalamus
  • MCH
  • Neuropeptide
  • Obesity

ASJC Scopus subject areas

  • Neuroscience(all)

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