The objectives of the proposed research are to identify and study factors that control ethanol reinforced behavior using mouse populations which have been bred selectively for high and low ethanol sensitivity. The methodology and principles of operant conditioning and pharmacogenetic analysis will be used. The studies will be limited to conditions where ethanol is taken orally and functions as a positive reinforcer. The focus will be on the variables that control ethanol reinforced behavior, especially genetic variables, but also including pharmacological variables, e.g., the interactions between ethanol and prostaglandins and how this affects ethanol drinking, and environmental variables, e.g., food deprivation/satiation and other dietary factors. Emphasis will be given to systematically studying variables of a range of values, and interactions among variables will be parametrically explored. For example, the effects of pretreatment with prostaglandin synthetase inhibitors on ethanol oral self-administration will be studied using a broad range of ethanol concentrations and fixed-ratio schedules. The proposed studies are important because 1) ethanol intake will be examined under conditions where it is taken orally and functions as a reinforcer; 2) they will explore genetic and environmental factors and their interactions which contribute to ethanol self-administration; 3) the use of the Long Sleep and Short Sleep mice will provide information concerning the degree of relationship between ethanol sensitivity in an acute situation and propensity to self-administer ethanol; and 4) the effects of pretreatment with prostaglandin synthetase inhibitors on ethanol oral self-administration will provide data about a specific biochemical system and its relationship to ethanol drinking. These studies will build upon an infrahuman model of ethanol reinforced behavior that we have developed in this laboratory, and will contribute to a systematized body of knowledge that will aid in the analysis of the complex problems of alcoholism and alcohol abuse.
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