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Saturday, July 7, 2012

The Use of a Novel Drinkometer System for Assessing Pharmacological Treatment Effects on Ethanol Consumption in Rats

There are numerous studies in the preclinical alcohol research field showing that pharmacological interventions and many other manipulations can influence ethanol (EtOH) consumption in a free-choice paradigm in rats. Most of these studies are based on 24-hour measurements. These studies provide a measure of the total amount of EtOH consumed per day, but do not provide information on the drinking patterns within this period of measurement. Here, we used a novel drinkometer system in combination with Fourier analysis to provide detailed information on drinking patterns.

Our automated drinkometer system measures fluid consumption by means of high-precision sensors attached to the drinking bottles in the home cage of the rat and thereby ameliorates several limitations of a classical lickometer-based drinkometer system. As an example of its application, we used the alcohol deprivation effect (ADE) model for relapse-like drinking and tested as a reference compound lamotrigine, which has a robust effect on the ADE. Fourier analysis was chosen as the main strategy for 24-hour drinking pattern recognition during water/EtOH drinking.

Under baseline conditions, voluntary EtOH consumption in rats can be expressed as characteristic oscillations that follow diurnal activity and differ in their amplitude, depending on the EtOH concentration. This diurnal drinking rhythmicity was altered during a relapse condition. Furthermore, lamotrigine given during the ADE did not significantly affect the drinking frequency or the number of approaches to the EtOH bottles when compared to vehicle-treated animals. However, EtOH intake during a drinking approach was dramatically reduced.

The use of the drinkometer system and mathematical modeling allows the characterization of treatment effects on relapse-like drinking with a great level of detail. One use of such detailed information may lie in its translational predictability. For instance, owing to lamotrigine treatment's lack of effect on EtOH drinking frequency or the number of approaches to the EtOH bottles, this compound might not be effective in relapse prevention per se but may reduce hedonic EtOH effects and could therefore be used in alcohol-dependent patients if harm reduction is the primary goal of treatment.

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