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.
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Acknowledgements
The authors would like to thank Armando Hernandez, Shannon Malesky, Ian McGraw, and Jeffrey Pressly for their excellent technical assistance. This work was supported by United States Public Health Service Grants R01DA029254, R01DA05018, T32DA031115 (DRM), and by a Senior Scientist Award K05DA17918 (CPF) from the National Institute on Drug Abuse, National Institutes of Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute on Drug Abuse or the National Institutes of Health.
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Maguire, D.R., Gerak, L.R. & France, C.P. Delay discounting of food and remifentanil in rhesus monkeys. Psychopharmacology 229, 323–330 (2013). https://doi.org/10.1007/s00213-013-3121-x
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DOI: https://doi.org/10.1007/s00213-013-3121-x