Assessment of alcohol craving and anti-craving drugs using the beer model in rats
Current pharmacotherapies for alcohol dependence in humans (e.g. Naltrexone, Acamprosate) are meeting with only limited therapeutic success. Our laboratory has developed the “beer model” of alcohol dependence and craving in an attempt to screen for novel therapeutic drugs and drug combinations that may have anti-craving potential. Rats have a remarkable appetite for beer and will drink much more beer than equivalent ethanol solutions in water. In the beer model, we give rats several weeks of access to beer or near-beer (a beer like beverage containing < 0.5% ethanol) in their home cages. The rats are then given limited daily access to beer or near-beer in a custom apparatus that delivers precise amounts of beer or near-beer to rats contingent upon the number of licks that they make. In some experiments a progressive ratio schedule is employed whereby rats have to emit an increasing number of licks for every drop of beer delivered. This can be readily used to measure the motivation rats have for beer. In other experiments, licking for beer is extinguished and factors causing reinstatement of the licking response have been examined. We have found that beer craving in rats is selectively reduced by the cannabinoid receptor antagonist SR 141716 and the opioid receptor antagonist naltrexone. Combining these two drugs appears to have a synergistic anti-craving effect. In other recent experiments we have examined the effects of topiramate in the beer model. Topiramate (20-80 mg/kg) proved to have only weak effects in decreasing the motivation for beer, and a much smaller effect than naltrexone. Other possible therapeutics for alcohol craving are currently under investigation in our laboratory.