The melanin-concentrating hormone-1 receptor modulates alcohol-induced reward and DARPP-32 phosphorylation
2016 (English)In: Psychopharmacology, ISSN 0033-3158, E-ISSN 1432-2072, Vol. 233, no 12, 2355-2363 p.Article in journal (Refereed) PublishedText
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.
Alcohol; Conditioned place preference (CPP); Knock-out mice; MCH1-R; p-DARPP-32; Reward
Pharmacology and Toxicology
IdentifiersURN: urn:nbn:se:liu:diva-129488DOI: 10.1007/s00213-016-4285-yISI: 000376410800013PubMedID: 27044354OAI: oai:DiVA.org:liu-129488DiVA: diva2:940499