Delay discounting of food and remifentanil in rhesus monkeys

Rationale Drug abuse can be conceptualized as choice between drug and nondrug reinforcers in which drug choice is excessive; factors impacting drug taking can be examined using procedures in which subjects choose between drug and an alternative reinforcer. Objective This experiment examined the effects of delayed reinforcement on choice between food and the mu-opioid receptor agonist remifentanil. Methods Rhesus monkeys responded under a concurrent fixed-ratio 5, fixed-ratio 5 schedule in which responding on one lever delivered one food pellet and responding on another lever delivered an i.v. infusion. Results With no delay, monkeys responded predominantly for food rather than saline or small doses of remifentanil; as the dose of remifentanil increased (0.1-1.0 mu g/kg/infusion), monkeys responded more for drug. Delaying delivery (30-240 s) of 0.32 and not 1.0 mu g/kg/infusion of remifentanil (food delivered immediately) decreased responding for drug and increased responding for food, resulting in a rightward shift in the remifentanil dose-effect curve. Delaying delivery of food (60-240 s) when doses of remifentanil smaller than 0.32 mu g/kg/infusion (but not saline) were available decreased responding for food and increased responding for drug, resulting in a leftward shift in the remifentanil dose-effect curve. Conclusion These results provide evidence that delaying the delivery of amu-opioid receptor agonist reduces its potency as a positive reinforcer; more importantly, delaying the delivery of an alternative nondrug reinforcer (e. g., food) enhances the reinforcing potency of the agonist. Thus, understanding the factors that control substance abuse requires examination of contingencies for both drug and nondrug reinforcers.