Mesolimbic exendin-4 attenuates reward salience evoked by neuropeptide Y and ghrelin

Behav Brain Res. 2023 Feb 25:440:114249. doi: 10.1016/j.bbr.2022.114249. Epub 2022 Dec 7.

Abstract

In the present study, we investigated the effects of the glucagon-like peptide-1 (GLP-1) agonist exendin-4 (Ex-4) on the stimulatory action of neuropeptide Y (NPY) and ghrelin. These effects were examined in relation to operant responding for palatable food or voluntary ethanol intake in a two-bottle limited access paradigm. Male Sprague Dawley rats, each with ventral tegmental area (VTA) unilateral guide cannulae, were used. Ex-4 was paired with either NPY, ghrelin, or combined NPY and ghrelin treatment. Our results indicated that while NPY and ghrelin reliably stimulated operant responding for sucrose pellets and increased ethanol intake, Ex-4 suppressed intake and, most importantly, significantly reduced the effects of NPY and ghrelin. Overall, this work provides compelling evidence that VTA GLP-1, NPY, and ghrelin systems interact within the brain to modulate reward salience.

Keywords: Alcohol; Ethanol; Glucagon-like Peptide 1 (GLP-1); Sucrose Pellet; Ventral Tegmental Area.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Ethanol / pharmacology
  • Exenatide* / pharmacology
  • Ghrelin* / pharmacology
  • Glucagon-Like Peptide 1 / pharmacology
  • Male
  • Neuropeptide Y* / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Reward*
  • Ventral Tegmental Area* / drug effects
  • Ventral Tegmental Area* / metabolism

Substances

  • Ethanol
  • Exenatide
  • Ghrelin
  • Glucagon-Like Peptide 1
  • Neuropeptide Y