title: Effects of melanocortin receptor ligands on ethanol intake and opioid peptide levels in alcohol-preferring AA rats.
abstract: Melanocortin (MC) peptides are suggested to play a role in opiate dependence, where they antagonise the addictive properties of opiates. To further study the involvement of the MCs in drug dependence, we analysed the effects of the MC(4)-receptor antagonist HS014 (1 nmol/rat), and the non-selective MC-receptor agonist MTII (1 nmol/rat), using i.c.v. administration, on ethanol intake in alcohol-preferring AA rats. The rats had access to ethanol during 40 days, resulting in a mean ethanol intake of 6.6 g/kg/day, before treatment. One group received only artificial cerebrospinal fluid solution. MTII caused a reduction in ethanol intake and ethanol preference, whereas HS014 was without effect. No effect on water intake was observed. A decrease in food intake was detected after MTII, whereas HS014 induced an increase in food intake. Analysis of dynorphin B and Met-enkephalin-Arg(6)Phe(7) immunoreactive levels revealed that MTII and HS014 altered opioid peptide levels in several brain areas and the pituitary gland of the rats with an established ethanol intake. This is the first report showing that manipulation of the MC-receptor system changes ethanol intake in chronically ethanol-drinking AA rats. In addition, manipulation of the MC system modulates ethanol-induced changes in opioid peptide levels.
authors.affiliation: Department of Pharmaceutical Biosciences, Division of Pharmacology, Uppsala University, Uppsala, Sweden. karolina.ploj@farmbio.uu.se
authors.forename: Karolina
authors.initials: K
authors.lastname: Ploj
authors.forename: Erika
authors.initials: E
authors.lastname: Roman
authors.forename: Ants
authors.initials: A
authors.lastname: Kask
authors.forename: Petri
authors.initials: P
authors.lastname: Hyytiä
authors.forename: Helgi B
authors.initials: HB
authors.lastname: Schiöth
authors.forename: Jarl E S
authors.initials: JE
authors.lastname: Wikberg
authors.forename: Ingrid
authors.initials: I
authors.lastname: Nylander
mesh_terms: D000428:Alcohol Drinking / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D004435:Eating / Q000187:drug effects / Q000502:physiology; D005260:Female; D008024:Ligands; D009842:Oligopeptides / Q000494:pharmacology / Q000627:therapeutic use; D018847:Opioid Peptides / Q000378:metabolism*; D010456:Peptides, Cyclic / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D018043:Receptors, Corticotropin / Q000819:agonists* / Q000037:antagonists & inhibitors* / Q000378:metabolism; D044101:Receptors, Melanocortin; D000521:alpha-MSH / Q000031:analogs & derivatives
chemical_list: C116941:HS014 cyclic peptide; D008024:Ligands; D009842:Oligopeptides; D018847:Opioid Peptides; D010456:Peptides, Cyclic; D018043:Receptors, Corticotropin; D044101:Receptors, Melanocortin; C105974:acetyl-norleucyl(4)-(aspartyl(5)-histidyl(6)-phenylalanyl(7)-arginyl(8)-tryptophyl(9)-lysyl(10))cyclo-alpha-MSH(4-10)amide; D000521:alpha-MSH