title: Glucagon-like Peptide-1 receptor signaling in the lateral parabrachial nucleus contributes to the control of food intake and motivation to feed.
abstract: Central glucagon-like peptide-1 receptor (GLP-1R) activation reduces food intake and the motivation to work for food, but the neurons and circuits mediating these effects are not fully understood. Although lateral parabrachial nucleus (lPBN) neurons are implicated in the control of food intake and reward, the specific role of GLP-1R-expressing lPBN neurons is unexplored. Here, neuroanatomical tracing, immunohistochemical, and behavioral/pharmacological techniques are used to test the hypothesis that lPBN neurons contribute to the anorexic effect of central GLP-1R activation. Results indicate that GLP-1-producing neurons in the nucleus tractus solitarius project monosynaptically to the lPBN, providing a potential endogenous mechanism by which lPBN GLP-1R signaling may exert effects on food intake control. Pharmacological activation of GLP-1R in the lPBN reduced food intake, and conversely, antagonism of GLP-1R in the lPBN increased food intake. In addition, lPBN GLP-1R activation reduced the motivation to work for food under a progressive ratio schedule of reinforcement. Taken together, these data establish the lPBN as a novel site of action for GLP-1R-mediated control of food intake and reward.
authors.affiliation: Department of Psychology, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Amber L
authors.initials: AL
authors.lastname: Alhadeff
authors.affiliation: Program in Neuroscience, Amherst College, Amherst, MA, USA.
authors.forename: John-Paul
authors.initials: JP
authors.lastname: Baird
authors.affiliation: Program in Neuroscience, Amherst College, Amherst, MA, USA.
authors.forename: Jennifer C
authors.initials: JC
authors.lastname: Swick
authors.affiliation: Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Hayes
authors.affiliation: Department of Psychology, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Harvey J
authors.initials: HJ
authors.lastname: Grill
mesh_terms: D000818:Animals; D001069:Appetite Regulation / Q000187:drug effects; D003216:Conditioning, Operant / Q000187:drug effects / Q000502:physiology; D059305:Diet, High-Fat; D004435:Eating / Q000187:drug effects; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism; D000067757:Glucagon-Like Peptide-1 Receptor; D008297:Male; D009042:Motivation / Q000187:drug effects / Q000502:physiology*; D009043:Motor Activity / Q000187:drug effects; D009434:Neural Pathways / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D065823:Parabrachial Nucleus / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D010842:Pica; D017207:Rats, Sprague-Dawley; D018027:Receptors, Glucagon / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012055:Reinforcement Schedule; D015398:Signal Transduction; D013569:Synapses / Q000187:drug effects / Q000502:physiology
chemical_list: C000593835:Glp1r protein, rat; D000067757:Glucagon-Like Peptide-1 Receptor; D018027:Receptors, Glucagon; D052216:Glucagon-Like Peptide 1