Ghrelin stimulates locomotor activity and accumbal dopamine-overflow via central cholinergic systems in mice: implications for its involvement in brain reward.
It is becoming increasingly apparent that there is a degree of neurochemical overlap between the reward systems and those regulating energy balance. We therefore investigated whether ghrelin, a stomach-derived and centrally derived orexigenic peptide, might act on the reward systems. Central ghrelin administration (1 microg/microL, to the third ventricle) induced an acute increase in locomotor activity as well as dopamine-overflow in the nucleus accumbens, suggesting that ghrelin can activate the mesoaccumbal dopamine system originating in the ventral tegmental area, a system associated with reward and motivated behaviour. The cholinergic afferents to the ventral tegmental area have been implicated in natural reward and in regulating mesoaccumbal dopamine neurons. The possibility that nicotinic receptors are involved in mediating the stimulatory and dopamine-enhancing effects of ghrelin is supported by the findings that peripheral injection of the unselective nicotinic antagonist mecamylamine (2.0 mg/kg) blocked these ghrelin-induced effects. Tentatively, ghrelin may, via activation of the acetylcholine-dopamine reward link, increase the incentive values of signals associated with motivated behaviours of importance for survival such as feeding behaviour. It will be important to discover whether this has therapeutic implications for compulsive addictive behaviours, such as eating behaviour disorders and drug dependence.
Jerlhag
Elisabet
E
Institute of Pharmacology and Physiology, Department of Pharmacology, Göteborg University, Sweden.
Egecioglu
Emil
E
Dickson
Suzanne L
SL
Andersson
Malin
M
Svensson
Lennart
L
Engel
Jörgen A
JA
D000344:Afferent Pathways / Q000187:drug effects / Q000503:physiopathology; D000818:Animals; D001921:Brain / Q000503:physiopathology*; D002799:Cholinergic Fibers / Q000187:drug effects* / Q000502:physiology; D004298:Dopamine / Q000378:metabolism*; D001068:Feeding and Eating Disorders / Q000503:physiopathology; D054439:Ghrelin; D007276:Injections, Intraventricular; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology; D051379:Mice; D008815:Mice, Inbred Strains; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000503:physiopathology; D036361:Peptide Hormones / Q000494:pharmacology*; D011978:Receptors, Nicotinic / Q000187:drug effects* / Q000502:physiology; D012201:Reward; D019966:Substance-Related Disorders / Q000503:physiopathology*; D013681:Tegmentum Mesencephali / Q000187:drug effects* / Q000502:physiology
D054439:Ghrelin; D036361:Peptide Hormones; D011978:Receptors, Nicotinic; D008464:Mecamylamine; D004298:Dopamine