Document Detail


Hippocampal GLP-1 Receptors Influence Food Intake, Meal Size, and Effort-Based Responding for Food Through Volume Transmission.
MedLine Citation:
PMID:  25035078     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Glucagon-like peptide-1 (GLP-1) is produced in the small intestines and in nucleus tractus solitarius (NTS) neurons. Activation of central GLP-1 receptors (GLP-1Rs) reduces feeding and body weight. The neural circuits mediating these effects are only partially understood. Here we investigate the inhibition of food intake and motivated responding for food in rats following GLP-1R activation in the ventral hippocampal formation (HPFv), a region only recently highlighted in food intake control. Increased HPFv GLP-1R activity following exendin-4 administration potently reduced food intake (both chow and Western diet) and body weight, whereas HPFv GLP-1R blockade increased food intake. These hypophagic effects were based on reduced meal size, and likely do not involve nausea as HPFv exendin-4 did not induce a conditioned flavor avoidance. HPFv GLP-1R activation also reduced effort-based responding for food under an operant progressive ratio reinforcement schedule, but did not affect food conditioned place preference expression. To investigate possible routes of HPFv GLP-1 signaling, immunohistochemical analysis revealed the absence of GLP-1 axon terminals in the HPFv, suggesting volume transmission as a mechanism of action. Consistent with this, the presence of active GLP-1 was detected in both the cerebral spinal fluid (CSF) and the HPFv. The source of CSF GLP-1 may be NTS GLP-1-producing neurons, as, 1) ~30% of NTS GLP-1 neurons colocalized with the retrograde tracer fluorogold following lateral ventricle fluorogold injection, and 2) GLP-1-immunoreactive axon terminals were observed adjacent to the ventricular ependymal layer. Collectively these findings illuminate novel neuronal and behavioral mechanisms mediating food intake reduction by GLP-1.Neuropsychopharmacology accepted article preview online, 18 July 2014; doi:10.1038/npp.2014.175.
Authors:
Ted M Hsu; Joel D Hahn; Vaibhav R Konanur; Ashley Lam; Scott E Kanoski
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-7-18
Journal Detail:
Title:  Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology     Volume:  -     ISSN:  1740-634X     ISO Abbreviation:  Neuropsychopharmacology     Publication Date:  2014 Jul 
Date Detail:
Created Date:  2014-7-18     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8904907     Medline TA:  Neuropsychopharmacology     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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