The proposed research concerns an animal model of drug abuse (intravenous drug self-administration with rats) which will be used to investigate a variable (deprivation) that has recently been shown to produce marked increases in drug self-administration. Food deprivation produces large increases in drug intake via the oral and intravenous routes in Prats and rhesus monkeys across a range of drugs from several pharmacological classes. These findings may have major theoretical and clinical significance with respect to the initiation, maintenance, termination and prevention of drug abuse; however, little is known about the nature of the food deprivation effect. The proposed experiments are designed to assess the interaction of the deprivation-satiation variable with other major determinants of drug self-administration to extend the generality of the phenomenon. A dose-effect function will be compared under deprivation and satiation conditions to determine whether food deprivation produces a parallel shift in the dose-response curve or whether food deprivation interacts with dose. Similarly, experiments will compare the effects of food deprivation-satiation under different schedules of reinforcement. In an attempt to explain the food deprivation effect three groups of experiments are proposed. The first will explore the possibility that interoceptive stimuli related to food deprivation elicit drug-seeking behavior by serving as discriminative or conditioned reinforcing stimuli. Second, a reward interaction hypothesis will be tested. The effect on drug intake of depriving rats of reinforcing substances other than food (e.g., saccharin) will be measured, and the effect of drug deprivation (e.g., cocaine) on food intake will be investigated. The third group of experiments will address the question of whether or not food deprivation increases the reinforcing efficacy of a drug. Second-order, fixed-interval and progressive ratio schedules will be used with a fixed amount of drug available only upon schedule completion. Responding leading to drug access will be compared under conditions of food satiation and deprivation. Increased effectiveness of brief stimuli associated with drug access in maintaining self-administration behavior will also serve as an indicator of increased reinforcing efficacy.