The role of orexin-A in food motivation, reward-based feeding behavior and food-induced neuronal activation in rats

Neuroscience. 2010 Apr 28;167(1):11-20. doi: 10.1016/j.neuroscience.2010.02.002. Epub 2010 Feb 8.


Consumption beyond homeostatic needs, referred to here as reward-based feeding behavior, is a central contributor to the current obesity epidemic worldwide. Importantly, reward-based feeding can be driven by palatability, the taste and texture of the food, as well as cues associated with the consumption of palatable foods. The hypothalamic orexin system regulates both diet preference and anticipation of food rewards making it a likely target to modulate reward-based feeding behavior. In the current manuscript we hypothesized that orexin signaling mediates food-motivated behaviors and reward-based feeding behavior. We further hypothesized that orexin neurons and targets of the orexin system become activated in response to cues associated with the consumption of palatable food. Data from these studies suggest that orexin signaling promotes progressive ratio responding for palatable foods while blockade of orexin signaling attenuates reward-based feeding of a high fat diet. In addition, cues linked to the consumption of chocolate, or the receipt of a daily meal, activate the orexin system and its target regions differentially. Collectively, these data suggest that orexin signaling mediates reward-based feeding behavior and, within specific target regions, may regulate cue-induced overconsumption of palatable foods.

Publication types

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

MeSH terms

  • Animals
  • Benzoxazoles / pharmacology
  • Brain / drug effects
  • Brain / physiology
  • Cacao
  • Central Nervous System Agents / pharmacology
  • Cues
  • Dietary Fats
  • Eating / drug effects
  • Eating / physiology
  • Feeding Behavior / drug effects
  • Feeding Behavior / physiology*
  • Food*
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Male
  • Motivation / drug effects
  • Motivation / physiology*
  • Naphthyridines
  • Neurons / drug effects
  • Neurons / physiology*
  • Neuropeptides / metabolism*
  • Orexin Receptors
  • Orexins
  • Rats
  • Rats, Long-Evans
  • Receptors, G-Protein-Coupled / antagonists & inhibitors
  • Receptors, G-Protein-Coupled / metabolism
  • Receptors, Neuropeptide / antagonists & inhibitors
  • Receptors, Neuropeptide / metabolism
  • Reward*
  • Urea / analogs & derivatives
  • Urea / pharmacology


  • 1-(2-methylbenzoxazol-6-yl)-3-(1,5)naphthyridin-4-yl urea
  • Benzoxazoles
  • Central Nervous System Agents
  • Dietary Fats
  • Intracellular Signaling Peptides and Proteins
  • Naphthyridines
  • Neuropeptides
  • Orexin Receptors
  • Orexins
  • Receptors, G-Protein-Coupled
  • Receptors, Neuropeptide
  • Urea