title: Evidence that Melanocortin Receptor Agonist Melanotan-II Synergistically Augments the Ability of Naltrexone to Blunt Binge-Like Ethanol Intake in Male C57BL/6J Mice.
abstract: BACKGROUND
  The nonselective opioid receptor antagonist, naltrexone (NAL), reduces alcohol (ethanol [EtOH]) consumption in animals and humans and is an approved medication for treating alcohol abuse disorders. Proopiomelanocortin (POMC)-derived melanocortin (MC) and opioid peptides are produced in the same neurons in the brain, and recent preclinical evidence shows that MC receptor (MCR) agonists reduce excessive EtOH drinking in animal models. Interestingly, there is a growing body of literature revealing interactions between the MC and the opioid systems in the modulation of pain, drug tolerance, and food intake.
  
  
  METHODS
  In the present report, a mouse model of binge EtOH drinking was employed to determine whether the MCR agonist, melanotan-II (MTII), would improve the effectiveness of NAL in reducing excessive binge-like EtOH drinking when these drugs were co-administered prior to EtOH access.
  
  
  RESULTS
  Both NAL and MTII blunt binge-like EtOH drinking and associated blood EtOH levels, and when administered together, a low dose of MTII (0.26 mg/kg) produces a 7.6-fold increase in the effectiveness of NAL in reducing binge-like EtOH drinking. Using isobolographic analysis, it is demonstrated that MTII increases the effectiveness of NAL in a synergistic manner.
  
  
  CONCLUSIONS
  The current observations suggest that activators of MC signaling may represent a new approach to treating alcohol abuse disorders and a way to potentially improve existing NAL-based therapies.
authors.affiliation: Department of Psychology, University of North Carolina, Chapel Hill, North Carolina.
authors.forename: Montserrat
authors.initials: M
authors.lastname: Navarro
authors.affiliation: Department of Psychology, Autonoma University de Chile, Santiago, Chile.
authors.forename: Francisca
authors.initials: F
authors.lastname: Carvajal
authors.affiliation: Department of Psychology, Autonoma University de Chile, Santiago, Chile.
authors.forename: Jose Manuel
authors.initials: JM
authors.lastname: Lerma-Cabrera
authors.affiliation: Department of Psychology, University of Almeria, Almeria, Spain.
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Cubero
authors.affiliation: Department of Psychology, University of North Carolina, Chapel Hill, North Carolina.
authors.forename: Mitchell J
authors.initials: MJ
authors.lastname: Picker
authors.affiliation: Department of Psychology, University of North Carolina, Chapel Hill, North Carolina.|Bowles Center for Alcohol Studies, University of North Carolina, Chapel Hill, North Carolina.
authors.forename: Todd E
authors.initials: TE
authors.lastname: Thiele
mesh_terms: D000818:Animals; D063425:Binge Drinking / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D000431:Ethanol / Q000008:administration & dosage*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009271:Naltrexone / Q000008:administration & dosage* / Q000097:blood; D009292:Narcotic Antagonists / Q000008:administration & dosage; D010456:Peptides, Cyclic / Q000008:administration & dosage* / Q000097:blood; D044101:Receptors, Melanocortin / Q000819:agonists*; D000521:alpha-MSH / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood
chemical_list: D009292:Narcotic Antagonists; D010456:Peptides, Cyclic; D044101:Receptors, Melanocortin; C079282:melanotan-II; D000431:Ethanol; D000521:alpha-MSH; D009271:Naltrexone
keywords: Binge-Like Drinking; MTII; Melanocortin; Naltrexone; Opioid; Synergistic