title: Melanin-Concentrating Hormone and Its MCH-1 Receptor: Relationship Between Effects on Alcohol and Caloric Intake.
abstract: Reward and energy homeostasis are both regulated by a network of hypothalamic neuropeptide systems. The melanin-concentrating hormone (MCH) and its MCH-1 receptor (MCH1-R) modulate alcohol intake, but it remains unknown to what extent this reflects actions on energy balance or reward. Here, we evaluated the MCH1-R in regulation of caloric intake and motivation to consume alcohol in states of escalated consumption.
  
  
  
  Rats had intermittent access (IA) to alcohol and were divided into high- and low-drinking groups. Food and alcohol consumption was assessed after administration of an MCH1-R antagonist, GW803430. Next, GW803430 was evaluated on alcohol self-administration in protracted abstinence induced by IA in high-drinking rats. Finally, the effect of GW803430 was assessed on alcohol self-administration in acute withdrawal in rats exposed to alcohol vapor. Gene expression of MCH and MCH1-R was measured in the hypothalamus and nucleus accumbens (NAc) in both acute and protracted abstinence.
  
  
  
  High-drinking IA rats consumed more calories from alcohol than chow and GW803430 decreased both chow and alcohol intake. In low-drinking rats, only food intake was affected. In protracted abstinence from IA, alcohol self-administration was significantly reduced by pretreatment with GW803430 and gene expression of both MCH and the MCH1-R were dysregulated in hypothalamus and NAc. In contrast, during acute withdrawal from vapor exposure, treatment with GW803430 did not affect alcohol self-administration, and no changes in MCH or MCH1-R gene expression were observed.
  
  
  
  Our data suggest a dual role of MCH and the MCH1-R in regulation of alcohol intake, possibly through mechanisms involving caloric intake and reward motivation. A selective suppression of alcohol self-administration during protracted abstinence by GW803430 was observed and accompanied by adaptations in gene expression of MCH and MCH1-R. Selective suppression of escalated consumption renders the MCH1-R an attractive target for treatment of alcohol use disorders.
authors: Department of Clinical and Experimental Medicine, Linkoping University, Linkoping, Sweden. camilla.s.karlsson@liu.se.
authors: Camilla
authors: C
authors: Karlsson
authors: Department of Clinical and Experimental Medicine, Linkoping University, Linkoping, Sweden.
authors: Abdul Maruf Asif
authors: AM
authors: Aziz
authors: Laboratory of Clinical and Translational Studies, NIAAA, NIH, Bethesda, Maryland.
authors: Faazal
authors: F
authors: Rehman
authors: Laboratory of Clinical and Translational Studies, NIAAA, NIH, Bethesda, Maryland.
authors: Caleb
authors: C
authors: Pitcairn
authors: Department of Clinical and Experimental Medicine, Linkoping University, Linkoping, Sweden.
authors: Riccardo
authors: R
authors: Barchiesi
authors: Department of Clinical and Experimental Medicine, Linkoping University, Linkoping, Sweden.
authors: Estelle
authors: E
authors: Barbier
authors: Department of Clinical and Experimental Medicine, Linkoping University, Linkoping, Sweden.
authors: Mikaela
authors: M
authors: Wendel Hansen
authors: CNS Research, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana.
authors: Don
authors: D
authors: Gehlert
authors: Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors: Pia
authors: P
authors: Steensland
authors: Department of Clinical and Experimental Medicine, Linkoping University, Linkoping, Sweden.
authors: Markus
authors: M
authors: Heilig
authors: Department of Clinical and Experimental Medicine, Linkoping University, Linkoping, Sweden.
authors: Annika
authors: A
authors: Thorsell
mesh_terms: D000428:Alcohol Drinking / Q000503:physiopathology*; D000818:Animals; D004435:Eating / Q000502:physiology; D002149:Energy Intake / Q000502:physiology*; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D007028:Hypothalamic Hormones / Q000096:biosynthesis / Q000502:physiology*; D007031:Hypothalamus / Q000378:metabolism; D008297:Male; D008543:Melanins / Q000096:biosynthesis / Q000502:physiology*; D009042:Motivation / Q000502:physiology*; D009714:Nucleus Accumbens / Q000378:metabolism; D010907:Pituitary Hormones / Q000096:biosynthesis / Q000502:physiology*; D011744:Pyrimidinones / Q000494:pharmacology; D051381:Rats; D017481:Receptors, Somatostatin / Q000037:antagonists & inhibitors / Q000502:physiology*; D012646:Self Administration; D013876:Thiophenes / Q000494:pharmacology
chemical_list: C540748:6-(4-chlorophenyl)-3-(3-methoxy-4-(2-pyrrolidin-1-ylethoxy)phenyl)-3H-thieno(3,2-d)pyrimidin-4-one; D007028:Hypothalamic Hormones; C491208:MCHR1 protein, rat; D008543:Melanins; D010907:Pituitary Hormones; D011744:Pyrimidinones; D017481:Receptors, Somatostatin; D013876:Thiophenes; C019463:melanin-concentrating hormone
keywords: Alcohol Escalation; Calorie Intake; Melanin-Concentrating Hormone Receptor-1; Motivation; Reward