Journal
DRUG AND ALCOHOL DEPENDENCE
Volume 117, Issue 2-3, Pages 126-131Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.drugalcdep.2011.01.010
Keywords
Nicotine; Ghrelin; Ghrelin receptors; Reward; Dopamine
Categories
Funding
- Swedish Research Council [K2006-21X-04247-33-3]
- Alcohol Research Council of the Swedish Alcohol Retailing Monopoly
- Swedish Brain Foundation
- foundations of Wilhelm and Martina Lundgren, Knut and Alice Wallenberg
- Adlerbert Research
- Thuring's, Langmanska art
- Torsten and Ragnar Soderberg, Magnus Bergvall foundation
- Swedish Society of Medicine
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Background: The orexigenic peptide ghrelin activates the reward systems, specifically the cholinergic-dopaminergic reward link, suggesting that ghrelin may increase the incentive salience of motivated behaviours such as food seeking. Moreover, central ghrelin signalling, involving the growth hormone secretagogue receptor 1A (GHS-R1A), is required for the rewarding properties, as measured by locomotor stimulation, accumbal dopamine release and conditioned place preference, of alcohol, cocaine as well as amphetamine. As the target circuits for other drugs of abuse, including nicotine, in the brain includes this reward link, we sought to determine whether the central ghrelin signalling system is involved in nicotine's activation of this system. Methods: This was investigated by studying the effects of peripheral administration of a GHS-R1A antagonist (JMV2959) on the nicotine-induced locomotor simulation, accumbal dopamine release and conditioned place preference. Results: In the present study we found that the ability of nicotine to increase the locomotor activity, accumbal dopamine release and to condition place preference were reduced in mice treated with a GHS-R1A antagonist. Conclusion: Thus GHS-R1A appears to be required not only for alcohol, cocaine and amphetamine-induced reward, but also for reward induced by nicotine. Our data suggest that the central ghrelin signalling system may constitute a novel potential target for treatment of drug dependence. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
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