PT  - JOURNAL ARTICLE
AU  - Dan Georgescu
AU  - Robert M. Sears
AU  - Jonathan D. Hommel
AU  - Michel Barrot
AU  - Carlos A. Bolaños
AU  - Donald J. Marsh
AU  - Maria A. Bednarek
AU  - James A. Bibb
AU  - Eleftheria Maratos-Flier
AU  - Eric J. Nestler
AU  - Ralph J. DiLeone
TI  - The Hypothalamic Neuropeptide Melanin-Concentrating Hormone Acts in the Nucleus Accumbens to Modulate Feeding Behavior and Forced-Swim Performance
AID  - 10.1523/JNEUROSCI.1714-04.2005
DP  - 2005 Mar 16
TA  - The Journal of Neuroscience
PG  - 2933--2940
VI  - 25
IP  - 11
4099  - http://www.jneurosci.org/content/25/11/2933.short
4100  - http://www.jneurosci.org/content/25/11/2933.full
SO  - J. Neurosci.2005 Mar 16; 25
AB  - 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.