Combined low dose treatment with opioid and cannabinoid receptor antagonists synergistically reduces the motivation to consume alcohol in rats.
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.
Gallate
Jason E
JE
School of Psychology, University of Sydney, 2006 Sydney, NSW, Australia.
Mallet
Paul E
PE
McGregor
Iain S
IS
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
D002186:Cannabinoids; D004338:Drug Combinations; D009292:Narcotic Antagonists; D010880:Piperidines; D011720:Pyrazoles; D009270:Naloxone; D009271:Naltrexone; C043161:naloxazine; D000077285:Rimonabant