Amylin receptor signaling in the ventral tegmental area is physiologically relevant for the control of food intake

Neuropsychopharmacology. 2013 Aug;38(9):1685-97. doi: 10.1038/npp.2013.66. Epub 2013 Mar 8.


The ability of amylin, a pancreatic β-cell-derived neuropeptide, to promote negative energy balance has been ascribed to neural activation at the area postrema. However, despite amylin binding throughout the brain, the possible role of amylin signaling at other nuclei in the control of food intake has been largely neglected. We show that mRNA for all components of the amylin receptor complex is expressed in the ventral tegmental area (VTA), a mesolimbic structure mediating food intake and reward. Direct activation of VTA amylin receptors reduces the intake of chow and palatable sucrose solution in rats. This effect is mediated by reductions in meal size and is not due to nausea/malaise or prolonged suppression of locomotor activity. VTA amylin receptor activation also reduces sucrose self-administration on a progressive ratio schedule. Finally, antagonist studies provide novel evidence that VTA amylin receptor blockade increases food intake and attenuates the intake-suppressive effects of a peripherally administered amylin analog, suggesting that amylin receptor signaling in the VTA is physiologically relevant for food intake control and potentially clinically relevant for the treatment of obesity.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amylin Receptor Agonists
  • Animals
  • Calcitonin / administration & dosage
  • Calcitonin / antagonists & inhibitors
  • Calcitonin / pharmacology
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Eating / drug effects
  • Eating / physiology*
  • Male
  • Microinjections
  • Motor Activity / drug effects
  • Nausea / chemically induced
  • Peptide Fragments / administration & dosage
  • Peptide Fragments / pharmacology
  • RNA, Messenger / metabolism
  • Rats
  • Receptors, Islet Amyloid Polypeptide / antagonists & inhibitors
  • Receptors, Islet Amyloid Polypeptide / metabolism
  • Receptors, Islet Amyloid Polypeptide / physiology*
  • Reinforcement Schedule
  • Reward
  • Self Administration
  • Sucrose / administration & dosage
  • Sucrose / pharmacology
  • Ventral Tegmental Area / drug effects
  • Ventral Tegmental Area / physiology*


  • Amylin Receptor Agonists
  • Peptide Fragments
  • RNA, Messenger
  • Receptors, Islet Amyloid Polypeptide
  • AC 187
  • Sucrose
  • salmon calcitonin
  • Calcitonin