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A stimulus-control account of regulated drug intake in rats

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Abstract

Rationale

Patterns of drug self-administration are often highly regular, with a consistent pause after each self-injection. This pausing might occur because the animal has learned that additional injections are not reinforcing once the drug effect has reached a certain level, possibly due to the reinforcement system reaching full capacity. Thus, interoceptive effects of the drug might function as a discriminative stimulus, signaling when additional drug will be reinforcing and when it will not.

Objective

This hypothetical stimulus control aspect of drug self-administration was emulated using a schedule of food reinforcement.

Materials and methods

Rats’ nose-poke responses produced food only when a cue light was present. No drug was administered at any time. However, the state of the light stimulus was determined by calculating what the whole-body drug level would have been if each response in the session had produced a drug injection. The light was only presented while this virtual drug level was below a specific threshold. A range of doses of cocaine and remifentanil were emulated using parameters based on previous self-administration experiments.

Results

Response patterns were highly regular, dose-dependent, and remarkably similar to actual drug self-administration.

Conclusion

This similarity suggests that the emulation schedule may provide a reasonable model of the contingencies inherent in drug reinforcement. Thus, these results support a stimulus control account of regulated drug intake in which rats learn to discriminate when the level of drug effect has fallen to a point where another self-injection will be reinforcing.

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Acknowledgments

This research was supported by the Intramural Research Program of the NIH, National Institute on Drug Abuse. Thanks to Jonathan Katz, who commented on the manuscript, and to Roy Wise, Serge Ahmed, and Vladimir Tsibulsky for sharing their views of regulated drug intake.

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Correspondence to Leigh V. Panlilio.

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Panlilio, L.V., Thorndike, E.B. & Schindler, C.W. A stimulus-control account of regulated drug intake in rats. Psychopharmacology 196, 441–450 (2008). https://doi.org/10.1007/s00213-007-0978-6

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  • DOI: https://doi.org/10.1007/s00213-007-0978-6

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