Endogenous Glucagon-like Peptide-1 Receptor Signaling in the Nucleus Tractus Solitarius is Required for Food Intake Control

Neuropsychopharmacology. 2017 Jun;42(7):1471-1479. doi: 10.1038/npp.2016.246. Epub 2016 Oct 26.


Alhough the glucagon-like peptide-1 (GLP-1) system is critical to energy balance control and is a target for obesity pharmacotherapies, the receptor-population-mediating effects of endogenous GLP-1 signaling are not fully understood. To address this, we developed a novel adeno-associated virus (AAV-GLP-1R) that utilizes short hairpin RNA to chronically knock down GLP-1 receptors (GLP-1R) in rats. As pharmacological studies highlight the hindbrain nucleus tractus solitarius (NTS) as a brain region important for GLP-1R-mediated effects on energy balance, AAV-GLP-1R was injected into the NTS to examine the role of endogenous NTS GLP-1R signaling in energy balance control. Chow intake and meal size were significantly increased following chronic NTS GLP-1R knockdown. In addition, NTS GLP-1R knockdown significantly increased self-administration of palatable food under both fixed and progressive ratio schedules of reinforcement. Collectively, these data demonstrate that endogenous NTS GLP-1R signaling is required for the control of food intake and motivation to feed, and provide a new strategy to investigate the importance of distinct GLP-1R populations in the control of a variety of functions.

MeSH terms

  • Adenoviridae
  • Animals
  • Conditioning, Operant / physiology
  • Eating / physiology*
  • Glucagon-Like Peptide-1 Receptor / antagonists & inhibitors
  • Glucagon-Like Peptide-1 Receptor / biosynthesis*
  • Male
  • Motivation / physiology*
  • Rats
  • Rats, Sprague-Dawley
  • Self Administration
  • Signal Transduction / physiology*
  • Solitary Nucleus / metabolism*


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