Sub-chronic Ghrelin Receptor Blockade Attenuates Alcohol- and Amphetamine-Induced Locomotor Stimulation in Mice.
OBJECTIVE
Ghrelin initially emerged as a gut-brain hormone controlling food intake, meal initiation and appetite mainly via hypothalamic circuits in both rodents and humans. The findings that ghrelin receptors (GHS-R1A) are expressed in reward-related areas, including the nucleus accumbens (NAc) and ventral tegmental area (VTA), suggest that ghrelin is a novel reward regulator. Indeed, ghrelin signalling mediates the rewarding and motivational properties of addictive drugs. In addition, daily co-administration of a GHS-R1A antagonist and various addictive drugs prevents the drug-induced locomotor sensitization in rats.


METHODS
The present series of experiment were designed to evaluate the effect of repeated pharmacological GHS-R1A suppression on drug-induced locomotor stimulation in more detail.


RESULTS
We showed that sub-chronic pre-treatment of the GHS-R1A antagonist, JMV2959, attenuated the ability of acute administration of alcohol as well as of amphetamine to stimulate locomotion. However, there was no effect of sub-chronic JMV2959 treatment on locomotor activity per se or on the expression of the GHS-R1A gene (Ghsr) in the VTA or the NAc compared with vehicle treatment. In addition, sub-chronic ghrelin treatment caused a locomotor sensitization.


CONCLUSIONS
While previous research has pinpointed ghrelin as an appetite regulator the present study together with previous studies suggest that ghrelin signalling modulates various reward-mediated behaviours in rodents. Collectively, this suggests that the GHS-R1A could be a key target for novel treatment strategies for addiction.
Department of Pharmacology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
Petra
P
Suchankova
Department of Pharmacology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
Jörgen A
JA
Engel
Department of Pharmacology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden elisabet.jerlhag@pharm.gu.se.
Elisabet
E
Jerlhag
D000661:Amphetamine / Q000008:administration & dosage*; D000818:Animals; D000697:Central Nervous System Stimulants / Q000008:administration & dosage; D000431:Ethanol / Q000008:administration & dosage*; D005998:Glycine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D008124:Locomotion / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051379:Mice; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D054440:Receptors, Ghrelin / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D014230:Triazoles / Q000008:administration & dosage*; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000378:metabolism
D000697:Central Nervous System Stimulants; C569751:N-(1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-aminoacetamide; D054440:Receptors, Ghrelin; D014230:Triazoles; D000431:Ethanol; D000661:Amphetamine; D005998:Glycine