Glucagon-like Peptide-1 receptor signaling in the lateral parabrachial nucleus contributes to the control of food intake and motivation to feed

Neuropsychopharmacology. 2014 Aug;39(9):2233-43. doi: 10.1038/npp.2014.74. Epub 2014 Mar 26.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Appetite Regulation* / drug effects
  • Conditioning, Operant / drug effects
  • Conditioning, Operant / physiology
  • Diet, High-Fat
  • Eating* / drug effects
  • Glucagon-Like Peptide 1 / metabolism
  • Glucagon-Like Peptide-1 Receptor
  • Male
  • Motivation / drug effects
  • Motivation / physiology*
  • Motor Activity / drug effects
  • Neural Pathways / cytology
  • Neural Pathways / drug effects
  • Neural Pathways / physiology
  • Neurons / cytology
  • Neurons / drug effects
  • Neurons / physiology*
  • Parabrachial Nucleus / cytology
  • Parabrachial Nucleus / drug effects
  • Parabrachial Nucleus / physiology*
  • Pica
  • Rats, Sprague-Dawley
  • Receptors, Glucagon / agonists
  • Receptors, Glucagon / antagonists & inhibitors
  • Receptors, Glucagon / metabolism*
  • Reinforcement Schedule
  • Signal Transduction
  • Synapses / drug effects
  • Synapses / physiology

Substances

  • Glp1r protein, rat
  • Glucagon-Like Peptide-1 Receptor
  • Receptors, Glucagon
  • Glucagon-Like Peptide 1