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Karlsson, C., Rehman, F., Damdazic, R., Atkins, A. L., Schank, J. R., Gehlert, D. R., . . . Heilig, M. (2016). The melanin-concentrating hormone-1 receptor modulates alcohol-induced reward and DARPP-32 phosphorylation. Psychopharmacology, 233(12), 2355-2363
Open this publication in new window or tab >>The melanin-concentrating hormone-1 receptor modulates alcohol-induced reward and DARPP-32 phosphorylation
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2016 (English)In: Psychopharmacology, ISSN 0033-3158, E-ISSN 1432-2072, Vol. 233, no 12, p. 2355-2363Article in journal (Refereed) Published
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
Alcohol; Conditioned place preference (CPP); Knock-out mice; MCH1-R; p-DARPP-32; Reward
National Category
Pharmacology and Toxicology
urn:nbn:se:liu:diva-129488 (URN)10.1007/s00213-016-4285-y (DOI)000376410800013 ()27044354 (PubMedID)
Available from: 2016-06-21 Created: 2016-06-20 Last updated: 2018-01-10

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