The proposed research aims to develop a behavioral laboratory model of drug craving in the mouse and to identify individual differences in craving behavior produced by differences in genetic endowment. The first specific goal is to examine a reward-seeking/self- administration paradigm with two inbred strains (Balb/c and C57Bl/6) and one outbred (CD-1) strain of mice. These initial studies will identify optimal parameters for measuring craving- related behaviors in addressing the second and fourth goals. Our second goal is to test the drug-seeking/ oral self-administration procedure using ethanol reward, the ethanol-consuming C57Bl/6 mice, and the anti-craving medication naltrexone. The third goal, to be accomplished in a new type of force plate movement analyzer, is to characterize sensitization and conditioned drugs effects of cocaine and amphetamine in the same three strains of mice. According to contemporary theories of drug abuse, sensitization and conditioned drug effects are key factors in craving and relapse, and our preliminary data with the force plate sensor suggest that conditioned drug effects and sensitization are measurable in terms of both spatial and temporal patterns of behavior. A fourth major goal is to develop a hybrid apparatus that incorporates both the operant methods and the force plate sensor so that reward-seeking behavior can be studied with both methods concurrently. In accomplishing the fourth goal all three strains of mice will be used. Throughout these studies, we will apply state-of-the-art computer recording techniques to the measurement of the physical characteristics of the instrumental response involved in reward- seeking and self-administration and quantify strain-specific sensitization and conditioned drug responses. Developing an animal model, such as this, will provide some of the basic information needed to understand how environmental context, individual differences in genetic endowment, and pharmacological variables influence drug craving, drug seeking and ultimately drug taking. In addition, future work with these methods should result in more effective pre-clinical evaluation of potentially effective treatment and prevention strategies of drug craving for a variety of abused drugs.
