Is addiction accompanied by an increase in the absolute reinforcing effect of a drug or the relative reinforcing effect of a drug, or both? The new research described in this proposal will attempt to answer this question in a search for substantive behavioral changes that occur as a function of chronic drug administration. The research will build on previous studies using intravenous drug self-administration in rhesus monkeys and behavioral economic evaluation of reinforcing effectiveness using demand curve elasticity measures. Demand for remifentanil or cocaine will be evaluated when the drugs are available for limited periods of time each day, and then when access to an opioid or a stimulant is increased to as much as two hours out of every six hours around the clock. Relative reinforcing effectiveness will be evaluated in studies where the monkeys can choose between drug and food under similar conditions of 2, 4, 6, and 8 hours per day of intermittent access to drug. Past research has demonstrated that monkeys increasingly choose remifentanil over cocaine in the presence of morphine withdrawal, and some animals show increased demand for both drugs during morphine withdrawal. Parallel studies will evaluate the effect of chronic administration of amphetamine on choice of remifentanil and cocaine under similar conditions of intoxication and withdrawal. It is hoped that a better understanding of the behavioral implications of chronic drug administration will assist in defining and quantifying addiction, and that this will serve as a touchstone for work designed to understand social and physiological correlates of addiction as well as behavioral and pharmacological interventions that are designed to reduce this excessive and destructive behavior.
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