Ghrelin receptor antagonism attenuates cocaine- and amphetamine-induced locomotor stimulation, accumbal dopamine release, and conditioned place preference

Psychopharmacology (Berl). 2010 Sep;211(4):415-22. doi: 10.1007/s00213-010-1907-7. Epub 2010 Jun 19.

Abstract

Introduction: Recently we demonstrated that genetic or pharmacological suppression of the central ghrelin signaling system, involving the growth hormone secretagogue receptor 1A (GHS-R1A), lead to a reduced reward profile from alcohol. As the target circuits for ghrelin in the brain include a mesolimbic reward pathway that is intimately associated with reward-seeking behaviour, we sought to determine whether the central ghrelin signaling system is required for reward from drugs of abuse other than alcohol, namely cocaine or amphetamine.

Results: We found that amphetamine-as well as cocaine-induced locomotor stimulation and accumbal dopamine release were reduced in mice treated with a GHS-R1A antagonist. Moreover, the ability of these drugs to condition a place preference was also attenuated by the GHS-R1A antagonist.

Conclusions: Thus GHS-R1A appears to be required not only for alcohol-induced reward, but also for reward induced by psychostimulant drugs. Our data suggest that the central ghrelin signaling system constitutes a novel potential target for treatment of addictive behaviours such as drug dependence.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amphetamine / pharmacology*
  • Animals
  • Behavior, Addictive / drug therapy
  • Behavior, Animal / drug effects
  • Cocaine / pharmacology*
  • Conditioning, Psychological / drug effects
  • Dopamine / metabolism*
  • Drug Delivery Systems
  • Male
  • Mice
  • Motor Activity / drug effects
  • Nucleus Accumbens / drug effects
  • Nucleus Accumbens / metabolism
  • Receptors, Ghrelin / antagonists & inhibitors*
  • Reward
  • Signal Transduction / drug effects

Substances

  • Receptors, Ghrelin
  • Amphetamine
  • Cocaine
  • Dopamine