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Preclinical Model for Ethanol-Mediated Behaviors PDF Print E-mail
Abstract for presentation at ISBRA 2006 World Congress on Alcohol Research

A Potential High-Throughput Preclinical Model for Screening Compounds Selective for Inhibiting Ethanol-mediated Behaviors

J.K. Richards, J. Simms, C. Fry & S.E. Bartlett.

Medications Development Group, Ernest Gallo Clinic & Research Center, Dept of Neurology, UCSF, Emeryville, CA 94608
The development of effective treatments for alcoholism is currently hindered by a number of factors. Most notably is the lack of a good model for validating lead compounds, a fact compounded by the length of time required to perform the currently employed models. Gallate & McGregor (1999) observed that rats will drink significantly more beer than unflavoured ethanol solutions with the same ethanol content and presented studies to show that ritanserin, naloxone and SR 141716 selectively reduced beer consumption. We have evaluated this model to determine if it would be a valuable preclinical tool to be used as a high throughput primary screen for potential lead compounds. We have found using a limited access 2 bottle choice beer/near beer paradigm that adult male Long Evans rats will consume 1.13 ± 0.08g/kg ethanol in 1 hour (after 1 day training, n=12), compared to 0.7 ± 0.4g/kg ethanol from a 10% solution (after 9 weeks training for limited access consumption, n=14) and 0.28 ± 0.03g/kg from a 4.5% ethanol solution (n=14). In the operant self administration paradigm we show that animals will self administer beer (0.7 ± 0.09 g/kg, n=3) and near beer immediately, reduced by pretreating with naltrexone (1 mg/kg), compared with 10% ethanol (0.5 ± 0.12 g/kg after 6-8 weeks training, n=8) thus negating the need for prolonged initial sucrose fade training. We also show that animals will reinstate for beer to previously associated cues, an important aspect for screening potential anti-relapse therapeutics. We have shown using the beer/near beer model of drinking that the protocol time is reduced by ~2 months compared with 10% ethanol alone. In addition, a much greater percentage of the animals will drink and in greater quantities, thus it provides a more robust signal:noise ratio for testing lead compounds.