Combined low dose treatment with opioid and cannabinoid receptor antagonists synergistically reduces the motivation to consume alcohol in rats
- First Online:
- 83 Downloads
Opioid and cannabinoid CB1 receptor antagonists reduce the motivation to consume alcohol when taken individually but their effectiveness in combination is not yet known.
The effects of naloxone/naltrexone and SR 141716 alone and in combination were examined on beer consumption in rats.
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 IP), SR 141716 (0.15, 0.3 or 0.6 mg/kg IP) 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.
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.
The combined, low dose treatment has possible clinical efficacy in treating alcohol craving in humans.
KeywordsSR 141716 Naloxone Naltrexone Rat Beer Alcohol Self-administration
- Arnone M, Maruani J, Chaperon F, Thiebot MH, Poncelet M, Soubrie P, Le Fur G (1997) Selective inhibition of sucrose and ethanol intake by SR 141716, an antagonist of central cannabinoid (CB1) receptors. Psychopharmacology 132:104–106Google Scholar
- Gallate JE, McGregor IS (1999) The motivation for beer in rats: effects of ritanserin, naloxone and SR 141716. Psychopharmacology 142:302–308Google Scholar
- Hartmann PM (1997) Naltrexone in alcohol dependence. Am Family Phys 55:1877–1879Google Scholar
- Kirkham TC, Williams CM (2001) Synergistic effects of opioid and cannabinoid antagonists on food intake. Psychopharmacology 153:267–270Google Scholar
- McGregor IS (1996) Using Strawberry Tree WorkbenchMac and Workbench PC software for data acquisition and control in the animal learning laboratory. Behav Res Meth Instr Comp 28:38–48Google Scholar
- Rezvani AH, Overstreet DH, Mason GA, Janowsky DS, Hamedi M, Clark E Jr, Yang Y (2000) Combination pharmacotherapy: a mixture of small doses of naltrexone, fluoxetine, and a thyrotropin-releasing hormone analogue reduces alcohol intake in three strains of alcohol-preferring rats. Alcohol Alcohol 35:76–83CrossRefPubMedGoogle Scholar