title: Combined low dose treatment with opioid and cannabinoid receptor antagonists synergistically reduces the motivation to consume alcohol in rats.
abstract: BACKGROUND
  Opioid and cannabinoid CB(1) receptor antagonists reduce the motivation to consume alcohol when taken individually but their effectiveness in combination is not yet known.
  
  
  OBJECTIVE
  The effects of naloxone/naltrexone and SR 141716 alone and in combination were examined on beer consumption in rats.
  
  
  METHODS
  In a progressive ratio paradigm rats were trained to lick at a tube for either beer (4.5% ethanol v/v) or near-beer (beer containing <0.5% ethanol v/v) under a progressive ratio schedule of reinforcement. They were then tested with naloxone (0.3, 0.6 or 1.2 mg/kg i.p.), SR 141716 (0.15, 0.3 or 0.6 mg/kg i.p.) and their combination. In a continuous access paradigm, other rats were given beer or near-beer in their home cages for several weeks and the effects of repeated (4 day) administration of naltrexone (0.3, 0.6 or 1.2 mg/kg), SR 141716 (0.15, 0.3 or 0.6 mg/kg) and their combination were assessed.
  
  
  RESULTS
  In the progressive ratio paradigm SR 141716, naloxone and their combination were more effective in reducing the break points for beer rather than near-beer. The two lowest dose combinations produced a synergistic reduction in break points. The highest dose combination reduced break points for both beer and near-beer and effects were more additive than synergistic. In the continuous access paradigm, the low doses of the drugs selectively reduced beer consumption in a synergistic fashion with higher doses having a less selective and more additive effect.
  
  
  CONCLUSIONS
  The combined, low dose treatment has possible clinical efficacy in treating alcohol craving in humans.
authors.affiliation: School of Psychology, University of Sydney, 2006 Sydney, NSW, Australia.
authors.forename: Jason E
authors.initials: JE
authors.lastname: Gallate
authors.forename: Paul E
authors.initials: PE
authors.lastname: Mallet
authors.forename: Iain S
authors.initials: IS
authors.lastname: McGregor
mesh_terms: D000428:Alcohol Drinking / Q000188:drug therapy* / Q000523:psychology; D000818:Animals; D002186:Cannabinoids / Q000037:antagonists & inhibitors*; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004357:Drug Synergism; D008297:Male; D009042:Motivation; D009270:Naloxone / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use*; D009271:Naltrexone / Q000494:pharmacology / Q000627:therapeutic use*; D009292:Narcotic Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D010880:Piperidines / Q000494:pharmacology / Q000627:therapeutic use; D011720:Pyrazoles / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D000077285:Rimonabant
chemical_list: D002186:Cannabinoids; D004338:Drug Combinations; D009292:Narcotic Antagonists; D010880:Piperidines; D011720:Pyrazoles; D009270:Naloxone; D009271:Naltrexone; C043161:naloxazine; D000077285:Rimonabant