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- Title
The melanin-concentrating hormone-1 receptor modulates alcohol-induced reward and DARPP-32 phosphorylation.
- Authors
Karlsson, Camilla; Rehman, Faazal; Damdazic, Ruslan; Atkins, Alison; Schank, Jesse; Gehlert, Donald; Steensland, Pia; Thorsell, Annika; Heilig, Markus
- Abstract
Rationale: 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. Methods: 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. Results: 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. Conclusion: Our results suggest that MCH1-Rs regulate the rewarding properties of alcohol through interactions with signaling cascades downstream of DA receptors in the NAcSh.
- Subjects
MELANIN-concentrating hormone; INGESTION; IMMUNOHISTOCHEMISTRY; DOPAMINE; LABORATORY mice
- Publication
Psychopharmacology, 2016, Vol 233, Issue 12, p2355
- ISSN
0033-3158
- Publication type
Article
- DOI
10.1007/s00213-016-4285-y