title: Hippocampal GLP-1 receptors influence food intake, meal size, and effort-based responding for food through volume transmission.
abstract: 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 cerebrospinal 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 (FG) following lateral ventricle FG 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.
authors.affiliation: 1] Neuroscience Program, University of Southern California, Los Angeles, CA, USA [2] Department of Biological Sciences, University of Southern California, Los Angeles, CA, USA.
authors.forename: Ted M
authors.initials: TM
authors.lastname: Hsu
authors.affiliation: Department of Biological Sciences, University of Southern California, Los Angeles, CA, USA.
authors.forename: Joel D
authors.initials: JD
authors.lastname: Hahn
authors.affiliation: Department of Biological Sciences, University of Southern California, Los Angeles, CA, USA.
authors.forename: Vaibhav R
authors.initials: VR
authors.lastname: Konanur
authors.affiliation: Neuroscience Program, University of Southern California, Los Angeles, CA, USA.
authors.forename: Ashley
authors.initials: A
authors.lastname: Lam
authors.affiliation: 1] Neuroscience Program, University of Southern California, Los Angeles, CA, USA [2] Department of Biological Sciences, University of Southern California, Los Angeles, CA, USA.
authors.forename: Scott E
authors.initials: SE
authors.lastname: Kanoski
mesh_terms: D000821:Animal Feed; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology; D001369:Axons / Q000187:drug effects / Q000502:physiology; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology; D004435:Eating / Q000187:drug effects / Q000502:physiology*; D000077270:Exenatide; D005247:Feeding Behavior / Q000187:drug effects / Q000502:physiology*; D000067757:Glucagon-Like Peptide-1 Receptor / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D007004:Hypoglycemic Agents / Q000494:pharmacology; D008297:Male; D009042:Motivation / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D010455:Peptides / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D012055:Reinforcement Schedule; D012249:Rhombencephalon / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D013037:Spatial Behavior / Q000187:drug effects / Q000502:physiology; D055697:Taste Perception / Q000187:drug effects / Q000502:physiology; D014688:Venoms / Q000494:pharmacology
chemical_list: D000067757:Glucagon-Like Peptide-1 Receptor; D007004:Hypoglycemic Agents; D010455:Peptides; D014688:Venoms; D000077270:Exenatide