The food intake-suppressive effects of glucagon-like peptide-1 receptor signaling in the ventral tegmental area are mediated by AMPA/kainate receptors

Elizabeth G. Mietlicki-Baase, Pavel I. Ortinski, Laura E. Rupprecht, Diana R. Olivos, Amber L. Alhadeff, R. Christopher Pierce, Matthew R. Hayes

Research output: Contribution to journalArticlepeer-review

100 Scopus citations

Abstract

Glucagon-like peptide-1 receptor (GLP-1R) activation in the ventral tegmental area (VTA) is physiologically relevant for the control of palatable food intake. Here, we tested whether the food intake-suppressive effects of VTA GLP-1R activation are mediated by glutamatergic signaling within the VTA. Intra-VTA injections of the GLP-1R agonist exendin-4 (Ex-4) reduced palatable high-fat food intake in rats primarily by reducing meal size; these effects were mediated in part via glutamatergic AMPA/kainate but not NMDA receptor signaling. Additional behavioral data indicated that GLP-1R expressed specifically within the VTA can partially mediate the intake- and body weight-suppressive effects of systemically administered Ex-4, offering the intriguing possibility that this receptor population may be clinically relevant for food intake control. Intra-VTA Ex-4 rapidly increased tyrosine hydroxylase levels within the VTA, suggesting that GLP-1R activation modulates VTA dopaminergic signaling. Further evidence for this hypothesis was provided by electrophysiological data showing that Ex-4 increased the frequency of AMPA-mediated currents and reduced the paired/pulse ratio in VTA dopamine neurons. Together, these data provide novel mechanisms by which GLP-1R agonists in the mesolimbic reward system control for palatable food intake.

Original languageEnglish (US)
Pages (from-to)E1367-E1374
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume305
Issue number11
DOIs
StatePublished - Dec 1 2013
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

Keywords

  • 2-amino-3-hydroxy-5-methyl-4-isoxazol propionic acid
  • Diabetes
  • Dopamine
  • Glucagon- like peptide-1
  • Glutamate
  • Obesity
  • Reward

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