Document Detail

Ghrelin signaling in the ventral hippocampus stimulates learned and motivational aspects of feeding via PI3K-Akt signaling.
MedLine Citation:
PMID:  22884970     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: The stomach-derived hormone ghrelin drives higher-order feeding processes related to food reward and food seeking via central nervous system signaling at its receptor (GHSR1A). The specific nuclei mediating these effects are only partially understood. Here, we use a rat model to examine whether ghrelin signaling in the ventral subregion of the hippocampus (VHPC), a brain substrate of recent interest in energy balance control, affects learned and motivational aspects of feeding behavior.
METHODS: The effects of VHPC ghrelin administration were examined on feeding-relevant behavioral paradigms, including meal pattern analysis, operant lever pressing for sucrose, and conditioned stimulus-induced feeding. The intracellular signaling and downstream neuronal pathways stimulated by VHPC GHSR1A activation were assessed with immunoblot analysis and behavioral pharmacology.
RESULTS: Ghrelin delivery to the VHPC but not the dorsal hippocampus increased food intake primarily by increasing meal frequency. Intra-VHPC ghrelin delivery also increased willingness to work for sucrose and increased spontaneous meal initiation in nondeprived rats after the presentation of a conditioned stimulus that previously signaled meal access when the rats were food-restricted. The food intake enhancing effects of VHPC ghrelin were blocked by co-administration of a phosphoinositide 3-kinase (PI3K) inhibitor (LY294002). Immunoblot analyses provided complementary support for ghrelin activated PI3K-Akt signaling in the VHPC and revealed that this activation is blunted with high-fat diet consumption. Other immunoblot results show that VHPC GHSR1A signaling activates downstream dopaminergic activity in the nucleus accumbens.
CONCLUSIONS: These findings illuminate novel neuronal and behavioral mechanisms mediating ghrelinergic control of cognitive aspects of feeding control.
Scott E Kanoski; Samantha M Fortin; Katie M Ricks; Harvey J Grill
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-08-11
Journal Detail:
Title:  Biological psychiatry     Volume:  73     ISSN:  1873-2402     ISO Abbreviation:  Biol. Psychiatry     Publication Date:  2013 May 
Date Detail:
Created Date:  2013-04-16     Completed Date:  2013-10-21     Revised Date:  2014-05-09    
Medline Journal Info:
Nlm Unique ID:  0213264     Medline TA:  Biol Psychiatry     Country:  United States    
Other Details:
Languages:  eng     Pagination:  915-23     Citation Subset:  IM    
Copyright Information:
Copyright © 2013 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
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MeSH Terms
Chromones / pharmacology
Eating / drug effects,  physiology
Enzyme Inhibitors / pharmacology
Feeding Behavior / drug effects,  physiology*
Ghrelin / metabolism*,  pharmacology
Hippocampus / drug effects,  metabolism*
Learning / drug effects,  physiology
Morpholines / pharmacology
Motivation / drug effects,  physiology
Phosphatidylinositol 3-Kinases / metabolism
Proto-Oncogene Proteins c-akt / metabolism
Rats, Sprague-Dawley
Receptors, Ghrelin / metabolism*
Signal Transduction / drug effects,  physiology*
Grant Support
Reg. No./Substance:
0/Chromones; 0/Enzyme Inhibitors; 0/Ghrelin; 0/Ghsr1a protein, rat; 0/Morpholines; 0/Receptors, Ghrelin; 154447-36-6/2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; EC 2.7.1.-/Phosphatidylinositol 3-Kinases; EC Proteins c-akt

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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