To examine whether the cognitive deficit observed in chronic alcoholics is because of the chronic exposure to alcohol or to a factor that contributes to the chronic alcohol use, working memory was evaluated under a delayed matching-to-position task in rats selectively bred for ethanol preference or nonpreference (iP/iNP, iHAD1/iLAD1, and iHAD2/iLAD2). Before the study on working memory, rats were studied under a progressive ratio schedule of food presentation to determine whether differences in motivation to respond for food existed between the alcohol-preferring and -nonpreferring strains. No such differences were observed. Under the delayed matching-toposition schedule, the length of the delay was titrated such that accuracy was maintained at approximately 80%, and the mean length of the delay for each experimental session provided a measure of working memory function. In two (iP/iNP and iHAD1/iLAD1) of the three pairs of selectively bred rats, nonpreference to ethanol was associated with better working memory performance. In the third pair of selectively bred rats (iHAD2/iLAD2), the relationship was reversed, with increased ethanol preference associated with better working memory function after saline administration. After ethanol administration, both the mean delay and the rate of responding were decreased in all six strains. Based upon an ED 50 analysis, there was little evidence of strain difference in sensitivity to ethanol on either parameter. Additional studies are needed to better understand the relationship between working memory and ethanol preference in these rats.Several studies have shown altered cognitive function, including memory disturbances, in humans who abuse ethanol and other drugs of abuse (Bowden et al., 2001;Rogers and Robbins, 2001;Block et al., 2002;Mintzer and Stitzer, 2002). However, it is not clear whether these differences existed before the abuse or whether the differences are the result of the abuse. One approach to answering this question is to examine working memory in alcohol-preferring (P) and alcohol-nonpreferring (NP) rats in both the absence and presence of ethanol.In 1974, Li and Lumeng began studies on an outbred strain of Wistar rats from the Walter Reed Army Institute of Research, Silver Spring, MD (Lumeng et al., 1977;Li et al., 1979Li et al., , 1981. These studies on gene-specific behavioral traits led to the development of the P and NP rat lines. Rats that were selected for breeding in the P line consumed in excess of 5 g/kg/day ethanol and demonstrated a better than 2:1 preference for ethanol over water. Rats selected for breeding in the NP line consumed less than 1.5 g/kg/day ethanol and did not exceed an ethanol-to-water preference of greater than 0.5:1. After approximately 30 generations of breeding, voluntary ethanol consumption of P rats averaged 9.2 Ϯ 0.4 g/kg/ day, whereas the NP rats consumed 1.9 Ϯ 0.7 g/kg/day. In addition, when given free access to food along with a choice of 10% ethanol or water, P rats consume 20 to 30% of their total calories ...