Psychopharmacology

, Volume 173, Issue 1, pp 210–216

Combined low dose treatment with opioid and cannabinoid receptor antagonists synergistically reduces the motivation to consume alcohol in rats

  • Jason E. Gallate
  • Paul E. Mallet
  • Iain S. McGregor
Original Investigation

DOI: 10.1007/s00213-003-1694-5

Cite this article as:
Gallate, J.E., Mallet, P.E. & McGregor, I.S. Psychopharmacology (2004) 173: 210. doi:10.1007/s00213-003-1694-5

Abstract

Rationale

Opioid and cannabinoid CB1 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 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.

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.

Keywords

SR 141716 Naloxone Naltrexone Rat Beer Alcohol Self-administration 

Copyright information

© Springer-Verlag 2003

Authors and Affiliations

  • Jason E. Gallate
    • 1
  • Paul E. Mallet
    • 2
  • Iain S. McGregor
    • 1
  1. 1.School of PsychologyUniversity of SydneySydneyAustralia
  2. 2.School of PsychologyUniversity of New EnglandArmidaleAustralia

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