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Interactions of cocaine with dopamine D2-like antagonists in squirrel monkeys

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Abstract

Rationale

Studies investigating dopamine D2 receptor antagonism of cocaine's discriminative stimulus effects have resulted in varied effects possibly due to the use of different antagonists, species, and procedures.

Objectives

The present study sought to further investigate D2 antagonism of cocaine's discriminative stimulus effects using a variety of D2 antagonists and multiple doses of the antagonists in combination with cocaine.

Methods

The benzamide D2 antagonists, eticlopride, raclopride, and sulpiride, and the butyrophenone D2 antagonists haloperidol and spiperone were administered alone and in combination with cocaine in squirrel monkeys trained to discriminate cocaine from saline under a fixed-ratio food reinforcement procedure.

Results

All the D2 antagonists, except haloperidol, antagonized the discriminative stimulus effects of the cocaine training dose. However, only the benzamide D2 antagonists produced significant rightward shifts in the cocaine discriminative stimulus dose–effect curve and they only did so within a narrow dose range and time after administration. In contrast, the D2 antagonists failed to antagonize the rate-suppressant effects of cocaine, and in some cases, cocaine appeared to antagonize the rate-suppressant effects of the antagonists.

Conclusions

The present results suggest (1) that D2 antagonism of cocaine's discriminative stimulus effects depends critically on the selected antagonist, antagonist dose, and time of administration, as well as how antagonism is assessed (i.e., in terms of effects on training dose or on the cocaine dose–effect curve), (2) that the maximal shift in cocaine's discriminative stimulus dose–effect curve possible with D2 antagonists under these procedures is ~two- to threefold, and (3) that different effects of cocaine are differentially sensitive to dopamine receptor antagonism.

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Acknowledgments

We are grateful for the expert technical assistance of Eric Adams in conducting these studies. These studies were supported by the Intramural Research Program of the Department of Health and Human Services, National Institutes of Health, National Institute on Drug Abuse.

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None.

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Authors and Affiliations

  1. Division of Behavioral Biology, Johns Hopkins University School of Medicine, 5510 Nathan Shock Drive, Suite 3000, Johns Hopkins Bayview Campus, Baltimore, MD, 21224-6823, USA

    Paul L. Soto

  2. Medications Discovery Research Branch, Psychobiology Section, DHHS/NIH/NIDA IRP, BRC, Room 06A707, 251 Bayview Boulevard, Suite 200, Baltimore, MD, 21224, USA

    Jonathan L. Katz

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  1. Paul L. Soto
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  2. Jonathan L. Katz
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Correspondence to Paul L. Soto.

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Soto, P.L., Katz, J.L. Interactions of cocaine with dopamine D2-like antagonists in squirrel monkeys. Psychopharmacology 226, 393–400 (2013). https://doi.org/10.1007/s00213-012-2914-7

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  • DOI: https://doi.org/10.1007/s00213-012-2914-7

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