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 Hommel, Michel Barrot, Carlos A. Bolaños, Donald J. Marsh, Maria A. Bednarek, James A. Bibb, Eleftheria Maratos-Flier, Eric J. Nestler, Ralph J. DiLeone

Research output: Contribution to journalArticle

231 Citations (Scopus)

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
StatePublished - Mar 16 2005
Externally publishedYes

Fingerprint

Nucleus Accumbens
Feeding Behavior
Neuropeptides
Appetitive Behavior
Neurons
Antidepressive Agents
Dynorphins
Food Deprivation
Cyclic AMP Response Element-Binding Protein
AMPA Receptors
Enkephalins
Glutamate Receptors
Hypothalamus
Rodentia
Dopamine
Homeostasis
Phosphorylation
melanin-concentrating hormone
Injections

Keywords

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

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

The hypothalamic neuropeptide melanin-concentrating hormone acts in the nucleus accumbens to modulate feeding behavior and forced-swim performance. / Georgescu, Dan; Sears, Robert M.; Hommel, Jonathan; Barrot, Michel; Bolaños, Carlos A.; Marsh, Donald J.; Bednarek, Maria A.; Bibb, James A.; Maratos-Flier, Eleftheria; Nestler, Eric J.; DiLeone, Ralph J.

In: Journal of Neuroscience, Vol. 25, No. 11, 16.03.2005, p. 2933-2940.

Research output: Contribution to journalArticle

Georgescu, D, Sears, RM, Hommel, J, Barrot, M, Bolaños, CA, Marsh, DJ, Bednarek, MA, Bibb, JA, Maratos-Flier, E, Nestler, EJ & DiLeone, RJ 2005, 'The hypothalamic neuropeptide melanin-concentrating hormone acts in the nucleus accumbens to modulate feeding behavior and forced-swim performance', Journal of Neuroscience, vol. 25, no. 11, pp. 2933-2940. https://doi.org/10.1523/JNEUROSCI.1714-04.2005
Georgescu, Dan ; Sears, Robert M. ; Hommel, Jonathan ; Barrot, Michel ; Bolaños, Carlos A. ; Marsh, Donald J. ; Bednarek, Maria A. ; Bibb, James A. ; Maratos-Flier, Eleftheria ; Nestler, Eric J. ; DiLeone, Ralph J. / The hypothalamic neuropeptide melanin-concentrating hormone acts in the nucleus accumbens to modulate feeding behavior and forced-swim performance. In: Journal of Neuroscience. 2005 ; Vol. 25, No. 11. pp. 2933-2940.
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