Exploring the Behavioral and Metabolic Phenotype Generated by Re-Introduction of the Ghrelin Receptor in the Ventral Tegmental Area

Int J Mol Sci. 2017 Apr 26;18(5):914. doi: 10.3390/ijms18050914.


Ghrelin receptor (Ghr-R) signaling in neurons of the ventral tegmental area (VTA) can modulate dopaminergic function and the reward-related effects of both palatable foods and drugs of abuse. In this study, we re-introduced the Ghr-R in VTA neurons in Ghr-R knockout mice (Ghr-RVTA mice) to specifically study the importance of the constitutively active Ghr-R for VTA neuronal signaling. Our results showed that re-introduction of the Ghr-R in the VTA had no impact on body weight or food intake under basal conditions. However, during novel environment stress Ghr-RVTA mice showed increased food intake and energy expenditure compared to Ghr-R knockout mice, demonstrating the significance of Ghr-R signaling in the response to stress. Ghr-RVTA mice also showed increased cocaine-induced locomotor activity compared to Ghr-R knockout mice, highlighting the importance of ghrelin signaling for the reward-related effects of activation of VTA neurons. Overall, our data suggest that re-introduction of the Ghr-R in the mesolimbic reward system of Ghr-R knockout mice increases the level of activation induced by both cocaine and novelty stress.

Keywords: cocaine sensitivity; energy expenditure; food anticipatory activity; ghrelin; ghrelin receptor; stress; ventral tegmental area.

MeSH terms

  • Animals
  • Behavior, Animal / physiology*
  • Body Weight
  • Dependovirus / genetics
  • Dopamine Plasma Membrane Transport Proteins / metabolism
  • Eating
  • Energy Metabolism
  • Genetic Vectors / genetics
  • Genetic Vectors / metabolism
  • Humans
  • Locomotion
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Oxygen Consumption
  • Receptors, Dopamine D2 / metabolism
  • Receptors, Ghrelin / deficiency
  • Receptors, Ghrelin / genetics
  • Receptors, Ghrelin / metabolism*
  • Tyrosine 3-Monooxygenase / metabolism
  • Ventral Tegmental Area / metabolism*


  • Dopamine Plasma Membrane Transport Proteins
  • Receptors, Dopamine D2
  • Receptors, Ghrelin
  • Tyrosine 3-Monooxygenase