The objectives of this research project are to examine the effects of behavioral history on cocaine self-administration. The behavioral effects of drugs, including reinforcing effects, have been shown to be influenced by behavioral (e.g., schedule of reinforcement) and pharmacological (e.g., drug dose) variables. In addition, a growing body of evidence suggests that factors other than those that currently maintain responding, e.g., an organisms behavioral history, can have profound and long-lasting influences on the rate-altering effects of drugs. However, no data exists regarding modification of the reinforcing effects of drugs by behavioral history. One purpose of the research proposed in the present grant application is to use animal subjects (rhesus monkeys) to examine whether behavioral history can affect the rate and pattern of cocaine-maintained behavior. Subjects will be exposed to schedules of reinforcement that generate high or low rates of responding. Subsequently, rates and patterns of responding will be studied under a fixed-interval (FI) schedule of cocaine presentation. Long-lasting changes in Fl responding as a function of previous schedule of reinforcement will be evidence for an effect of history on drug-maintained behavior. To extend the generality of these findings, other experiments will examine whether a history of responding maintained by a nondrug reinforcer can similarly modify cocaine-maintained responding. A second series of experiments is designed to use a progressive-ratio schedule to examine whether behavioral history can modify the strength of cocaine as a positive reinforcer (i.e., cocaine's reinforcing efficacy). These experiments will examine whether the break point for cocaine (a measure of reinforcing efficacy) can be modified by a behavioral history involving responding for either a drug or nondrug reinforcer under various schedules of reinforcement. Changes in break point as a result of exposure to a particular schedule of reinforcement will be evidence that behavioral history can modify the reinforcing efficacy of cocaine. If the rate and pattern of drug-maintained behavior, as well as the efficacy of a drug as a positive reinforcer, vary with an individual's behavioral history, then knowledge of such historical variables may be important in understanding the etiology, maintenance, treatment and prevention of drug abuse.
