Combined low dose treatment with opioid and cannabinoid receptor antagonists synergistically reduces the motivation to consume alcohol in rats
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- Gallate, J.E., Mallet, P.E. & McGregor, I.S. Psychopharmacology (2004) 173: 210. doi:10.1007/s00213-003-1694-5
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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.