The objectives of the proposed research are to identify and study factors that control ethanol-reinforced behavior using several inbred mouse and rat populations which have been shown to differ in various measures of ethanol-related phenotypes, as well as rodent lines selectively bred for differences in ethanol-related traits. The methodology and principles or operant conditioning and pharmacogenetic analysis will be used. The self- administration 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 and environmental variables. In addition, the relationship between ethanol self-administration and other ethanol- related variables, primarily preference, but also withdrawal and neurosensitivity, will be examined to ascertain the degree of common genetic control among these factors. Emphasis will be given to systematically studying variables over a range of values, and interactions among variables will be parametrically explored. The proposed studies are important because 1) ethanol intake will be examined under conditions where it is taken orally and functions as a positive reinforcer; 2) they will explore genetic and environmental factors and their interactions which contribute to ethanol self-administration; 3) they will provide a substantive body of information concerning the degree of relationship between ethanol preference, propensity to self-administer ethanol using operant techniques, sensitivity to ethanol, and severity of ethanol withdrawal syndrome; and 4) the examination of ethanol's effects on schedule controlled responding across several genotypes will help to establish the relationship between sensitivity to ethanol as defined by acute behavioral tasks with ethanol-induced changes in responding under various operant paradigms. These studies will build upon a pharmacogenetic animal model of ethanol reinforced behavior which our laboratory has developed, 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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