Ghrelin receptor antagonism attenuates cocaine- and amphetamine-induced locomotor stimulation, accumbal dopamine release, and conditioned place preference.
BACKGROUND
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.
Jerlhag
Elisabet
E
Section for Pharmacology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, SE-405 30, Gothenburg, Sweden. elisabet.jerlhag@pharm.gu.se
Egecioglu
Emil
E
Dickson
Suzanne L
SL
Engel
Jörgen A
JA
D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D016739:Behavior, Addictive / Q000188:drug therapy; D001522:Behavior, Animal / Q000187:drug effects; D003042:Cocaine / Q000494:pharmacology*; D003213:Conditioning, Psychological / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism*; D016503:Drug Delivery Systems; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D054440:Receptors, Ghrelin / Q000037:antagonists & inhibitors*; D012201:Reward; D015398:Signal Transduction / Q000187:drug effects
D054440:Receptors, Ghrelin; D000661:Amphetamine; D003042:Cocaine; D004298:Dopamine