Opioid receptor involvement in the effect of AgRP- (83-132) on food intake and food selection

Am J Physiol Regul Integr Comp Physiol. 2001 Mar;280(3):R814-21. doi: 10.1152/ajpregu.2001.280.3.R814.

Abstract

Agouti-related peptide (AgRP) is a receptor antagonist of central nervous system (CNS) melanocortin receptors and appears to have an important role in the control of food intake since exogenous CNS administration in rats and overexpression in mice result in profound hyperphagia and weight gain. Given that AgRP is heavily colocalized with neuropeptide Y (NPY) and that orexigenic effects of NPY depend on activity at opioid receptors, we hypothesized that AgRP's food-intake effects are also mediated by opioid receptors. Subthreshold doses of the opioid receptor antagonist naloxone blocked AgRP-induced intake when given simultaneously but not 24 h after AgRP injection. Opioids not only influence food intake but food selection as well. Hence, we tested AgRP's effect to alter food choice between matched diets with differing dietary fat content. AgRP selectively enhanced intake of the high-fat but not the low-fat diet. Additionally, AgRP selectively increased chow intake in rats given ad libitum access to a 20% sucrose solution and standard rat chow. The current results indicate that AgRP influences not only caloric intake but food selection as well and that the early effects of AgRP depend critically on an interaction with opioid receptors.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Agouti-Related Protein
  • Animals
  • Dietary Fats / administration & dosage
  • Dietary Sucrose / administration & dosage
  • Dose-Response Relationship, Drug
  • Eating / drug effects*
  • Energy Intake
  • Food Preferences / drug effects*
  • Intercellular Signaling Peptides and Proteins
  • Male
  • Naloxone / administration & dosage
  • Naloxone / pharmacology
  • Narcotic Antagonists / pharmacology
  • Peptide Fragments / pharmacology
  • Proteins / pharmacology*
  • Rats
  • Rats, Long-Evans
  • Receptors, Opioid / physiology*
  • Solutions

Substances

  • Agouti-Related Protein
  • Dietary Fats
  • Dietary Sucrose
  • Intercellular Signaling Peptides and Proteins
  • Narcotic Antagonists
  • Peptide Fragments
  • Proteins
  • Receptors, Opioid
  • Solutions
  • Naloxone