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The melanin-concentrating hormone-1 receptor modulates alcohol-induced reward and DARPP-32 phosphorylation
Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
NIH, MD 20892 USA.
NIH, MD 20892 USA.
Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.ORCID iD: 0000-0002-9673-8442
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2016 (English)In: Psychopharmacology, ISSN 0033-3158, E-ISSN 1432-2072, Vol. 233, no 12, 2355-2363 p.Article in journal (Refereed) PublishedText
Abstract [en]

Melanin-concentrating hormone (MCH) is involved in the regulation of food intake and has recently been associated with alcohol-related behaviors. Blockade of MCH-1 receptors (MCH1-Rs) attenuates operant alcohol self-administration and decreases cue-induced reinstatement, but the mechanism through which the MCH1-R influences these behaviors remains unknown. MCH1-Rs are highly expressed in the nucleus accumbens shell (NAcSh) where they are co-expressed with dopamine (DA) receptors. MCH has been shown to potentiate responses to dopamine and to increase phosphorylation of DARPP-32, an intracellular marker of DA receptor activation, in the NAcSh. In the present study, we investigated the role of the MCH1-R in alcohol reward using the conditioned place preference (CPP) paradigm. We then used immunohistochemistry (IHC) to assess activation of downstream signaling after administration of a rewarding dose of alcohol. We found that alcohol-induced CPP was markedly decreased in mice with a genetic deletion of the MCH1-R as well as after pharmacological treatment with an MCH1-R antagonist, GW803430. In contrast, an isocaloric dose of dextrose did not produce CPP. The increase in DARPP-32 phosphorylation seen in wildtype (WT) mice after acute alcohol administration in the NAcSh was markedly reduced in MCH1-R knock-out (KO) mice. Our results suggest that MCH1-Rs regulate the rewarding properties of alcohol through interactions with signaling cascades downstream of DA receptors in the NAcSh.

Place, publisher, year, edition, pages
SPRINGER , 2016. Vol. 233, no 12, 2355-2363 p.
Keyword [en]
Alcohol; Conditioned place preference (CPP); Knock-out mice; MCH1-R; p-DARPP-32; Reward
National Category
Pharmacology and Toxicology
Identifiers
URN: urn:nbn:se:liu:diva-129488DOI: 10.1007/s00213-016-4285-yISI: 000376410800013PubMedID: 27044354OAI: oai:DiVA.org:liu-129488DiVA: diva2:940499
Available from: 2016-06-21 Created: 2016-06-20 Last updated: 2016-06-21

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Karlsson, CamillaAtkins, Alison LynnThorsell, AnnikaHeilig, Markus
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Division of Neuro and Inflammation ScienceFaculty of Medicine and Health SciencesDivision of Cell Biology
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