Drinking of high concentrations of ethanol versus palatable fluids in alcohol-preferring (P) rats: valid animal model of alcoholism

A genetically based animal model of alcoholism has been characterized in Wistar-derived rats in terms of their preference (P rats) or lack of preference (NP rats) for 10% ethanol over water. The present experiments were designed to determine: 1) whether a.10% solution of ethanol is the optimal concentration for differentiation of these lines: 2) what concentrations of ethanol are maximally preferred by P and NP rats; and 3) whether highly palatable fluids presented simultaneously with each rat's preferred solution of ethanol would alter the patterns of drinking by either the P or NP or both lines of rats. A three-bottle procedure was used to establish preference for ethanol in the presence of water as well as highly palatable solutions. The results showed that, when concentrations ranging from 3–30% were presented over a 12-day test interval, the mean absolute intake of ethanol of the P rats was 6.7 g/kg per day, with a maximum intake of 10.9 g/kg per day at the 25% concentration. These levels of intake wee significantly higher than the 4.3 g/kg per day consumed during the presentation of the commonly used constant concentration of 10%. Similarly, the mean absolute intake of ethanol by the NP rats was also elevated significantly at concentrations of 15–30% (2.0 g/kg per day) above the consumed at the 10% concentration (0.4 g/kg). The mean absolute intake by each P rat of the maximally preferred solution of ethanol tested in the presence of an artificially sweetened fluid (Nutrasweet) or a nurtitionally fortified, highly palatable chocolate drink (Slender) rose to 7.8 and 7.7 g/kg per day, respectively, which was significantly higher than the mean intakes during the 10 and 3–30% preference tests. Thus, P rats show a preference for pharmacologically significant amounts of ethanol at concentrations above the commonly used 10%, which is sustained when an alternative highly preferred palatable fluid is simultaneously available. Therefore, on the basis of previous studies and the present findings on the profile of ethanol self-selection, it is concluded that the P line of rats clearly represents a valid genetic animal model of alcoholism. Furthermore, because the profile of drinking of the P rat closely resembles that of rats injected intracerebrally with THP or 6-hydroxydopamine (6-OHDA), it is envisaged that a common neurochemical perturbation of the mesolimbic dopaminergic system may underlie the aberrant consumption of ethanol by these animals.