Delay discounting of food and remifentanil in rhesus monkeys

Abstract

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 μg/kg/infusion), monkeys responded more for drug. Delaying delivery (30-240 s) of 0.32 and not 1.0 μg/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 μg/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 a mu-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.

Figure 1

The number of reinforcers (infusions, closed circles; food pellets, open circles) received, when both reinforcers were available immediately, plotted as a function of dose of remifentanil (μg/kg/infusion) for individual monkeys. Each data point represents the mean (± range) from the last 3 sessions under each condition. “S” = saline.

Figure 2

The percentage choice for drug (number of infusions divided by total reinforcers received * 100) plotted as a function of delay (sec) to the delivery of 0.32 (circles) or 1.0 (squares) μg/kg/infusion of remifentanil. Each data point represents the mean (± range) from the last 3 sessions under each condition.

Figure 3

The percentage choice for drug or saline plotted as a function of delay (sec) to food delivery when the immediately available alternative was saline (circles), 0.01 (upright triangles), 0.032 (inverted triangles), or 0.1 (diamonds) μg/kg/infusion of remifentanil. See Figure 2 for other details.

Figure 4

The percentage choice for drug plotted as a function of dose of remifentanil when both reinforcers were available immediately (circles), when food was delayed by 120 sec (upright triangles), and when drug was delayed either 120 sec (inverted triangles; monkeys EL and ME) or 240 sec (diamonds; monkey GA). See Figure 2 for other details.