title: The melanin-concentrating hormone-1 receptor modulates alcohol-induced reward and DARPP-32 phosphorylation.
abstract: 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.
authors.affiliation: Department of Clinical and Experimental Medicine, Linkopings University, Linkoping, Sweden.
authors.forename: Camilla
authors.initials: C
authors.lastname: Karlsson
authors.affiliation: Laboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism (NIAAA), National Institutes of Health (NIH), Bethesda, MD, USA.
authors.forename: Faazal
authors.initials: F
authors.lastname: Rehman
authors.affiliation: Laboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism (NIAAA), National Institutes of Health (NIH), Bethesda, MD, USA.
authors.forename: Ruslan
authors.initials: R
authors.lastname: Damadzic
authors.affiliation: Department of Clinical and Experimental Medicine, Linkopings University, Linkoping, Sweden.
authors.forename: Alison L
authors.initials: AL
authors.lastname: Atkins
authors.affiliation: Department of Physiology and Pharmacology, University of Georgia, Athens, GA, USA.
authors.forename: Jesse R
authors.initials: JR
authors.lastname: Schank
authors.affiliation: Neuroscience and Endocrine Discovery Research, Lilly Research Laboratories, a Division of Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: Donald R
authors.initials: DR
authors.lastname: Gehlert
authors.affiliation: Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Pia
authors.initials: P
authors.lastname: Steensland
authors.affiliation: Department of Clinical and Experimental Medicine, Linkopings University, Linkoping, Sweden.
authors.forename: Annika
authors.initials: A
authors.lastname: Thorsell
authors.affiliation: Department of Clinical and Experimental Medicine, Linkopings University, Linkoping, Sweden. markus.heilig@liu.se.
authors.forename: Markus
authors.initials: M
authors.lastname: Heilig
mesh_terms: D000818:Animals; D003213:Conditioning, Psychological / Q000187:drug effects* / Q000502:physiology; D004298:Dopamine / Q000378:metabolism; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32 / Q000378:metabolism*; D004435:Eating / Q000187:drug effects / Q000502:physiology; D000431:Ethanol / Q000008:administration & dosage*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism*; D010766:Phosphorylation / Q000502:physiology; D017481:Receptors, Somatostatin / Q000502:physiology*; D012201:Reward; D012646:Self Administration
chemical_list: D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; C491209:Mchr1 protein, mouse; C497929:Ppp1r1b protein, mouse; D017481:Receptors, Somatostatin; D000431:Ethanol; D004298:Dopamine
keywords: Alcohol; Conditioned place preference (CPP); Knock-out mice; MCH1-R; Reward; p-DARPP-32