The objectives of the proposed research are to study and identify factors that control drug reinforced behavior. The methodology and principles of operant conditioning will be used. The studies will be limited to drugs that are taken orally and that function as positive reinforcers. Subjects will be rhesus monkeys, rats, and mice. In the upcoming years the principal focus will be on variables that control drug reinforced behavior such as reinforcement schedules, food deprivation, and alternative reinforcers. Genetic factors, specifically strain differences, will be studied. Consequences of drug taking behavior (tolerance and physiological dependence) will also be examined within a context whereby the drug is taken by mouth and functions as a reinforcer. Special emphasis will be given to systematically studying variables over a range of values, and interactions among variables will be parametically explored. For example, the effects of fixed-ratio size will be examined using a broad range of drug concentrations. These studies will build upon an infrahuman model of oral drug dependence that we have developed in this laboratory. The proposed studies will provide an organized group of findings that will complement and extend results obtained by others using the intravenous route. These types of laboratory studies of drug taking behavior will contribute to a systematized body of knowledge that will aid in the analysis of the complicated problem of human drug dependence.