Document Detail

Regulation of nucleus accumbens activity by the hypothalamic neuropeptide melanin-concentrating hormone.
MedLine Citation:
PMID:  20554878     Owner:  NLM     Status:  MEDLINE    
The lateral hypothalamus and the nucleus accumbens shell (AcbSh) are brain regions important for food intake. The AcbSh contains high levels of receptor for melanin-concentrating hormone (MCH), a lateral hypothalamic peptide critical for feeding and metabolism. MCH receptor (MCHR1) activation in the AcbSh increases food intake, while AcbSh MCHR1 blockade reduces feeding. Here biochemical and cellular mechanisms of MCH action in the rodent AcbSh are described. A reduction of phosphorylation of GluR1 at serine 845 (pSer(845)) is shown to occur after both pharmacological and genetic manipulations of MCHR1 activity. These changes depend upon signaling through G(i/o), and result in decreased surface expression of GluR1-containing AMPA receptors (AMPARs). Electrophysiological analysis of medium spiny neurons (MSNs) in the AcbSh revealed decreased amplitude of AMPAR-mediated synaptic events (mEPSCs) with MCH treatment. In addition, MCH suppressed action potential firing MSNs through K(+) channel activation. Finally, in vivo recordings confirmed that MCH reduces neuronal cell firing in the AcbSh in freely moving animals. The ability of MCH to reduce cell firing in the AcbSh is consistent with a general model from other pharmacological and electrophysiological studies whereby reduced AcbSh neuronal firing leads to food intake. The current work integrates the hypothalamus into this model, providing biochemical and cellular mechanisms whereby metabolic and limbic signals converge to regulate food intake.
Robert M Sears; Rong-Jian Liu; Nandakumar S Narayanan; Ruth Sharf; Mark F Yeckel; Mark Laubach; George K Aghajanian; Ralph J DiLeone
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of neuroscience : the official journal of the Society for Neuroscience     Volume:  30     ISSN:  1529-2401     ISO Abbreviation:  J. Neurosci.     Publication Date:  2010 Jun 
Date Detail:
Created Date:  2010-06-17     Completed Date:  2010-07-02     Revised Date:  2013-05-29    
Medline Journal Info:
Nlm Unique ID:  8102140     Medline TA:  J Neurosci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  8263-73     Citation Subset:  IM    
Department of Psychiatry, Ribicoff Research Facilities, Yale University School of Medicine, New Haven, Connecticut 06508, USA.
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MeSH Terms
Action Potentials / drug effects,  genetics
Barium Compounds / pharmacology
Biotin / analogs & derivatives,  metabolism
Chlorides / pharmacology
Dopamine and cAMP-Regulated Phosphoprotein 32 / metabolism
Dose-Response Relationship, Drug
Enzyme Inhibitors / pharmacology
Excitatory Postsynaptic Potentials / drug effects,  physiology
Gene Expression Regulation / drug effects
Hypothalamic Hormones / genetics,  metabolism*,  pharmacology
Hypothalamus / cytology,  metabolism*
Melanins / genetics,  metabolism*,  pharmacology
Mice, Transgenic
Neural Pathways / physiology
Neurons / classification,  cytology,  drug effects,  physiology
Nucleus Accumbens / cytology,  physiology*
Patch-Clamp Techniques / methods
Pituitary Hormones / genetics,  metabolism*,  pharmacology
Potassium Channel Blockers / pharmacology
Rats, Long-Evans
Rats, Wistar
Receptors, AMPA / genetics,  metabolism
Serine / metabolism
Signal Transduction / drug effects,  physiology
Grant Support
DK073677/DK/NIDDK NIH HHS; R01 DK073677-04/DK/NIDDK NIH HHS; R01 MH067830-04/MH/NIMH NIH HHS; RL1 AA017536-05/AA/NIAAA NIH HHS
Reg. No./Substance:
0/Barium Compounds; 0/Chlorides; 0/Dopamine and cAMP-Regulated Phosphoprotein 32; 0/Enzyme Inhibitors; 0/Hypothalamic Hormones; 0/Melanins; 0/Pituitary Hormones; 0/Potassium Channel Blockers; 0/Receptors, AMPA; 0/glutamate receptor ionotropic, AMPA 1; 0/neurobiotin; 0VK51DA1T2/barium chloride; 56-45-1/Serine; 58-85-5/Biotin; 67382-96-1/melanin-concentrating hormone

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