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Effects of chronic d-amphetamine administration on the reinforcing strength of cocaine in rhesus monkeys

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Abstract

Rationale

Agonist medications have been proven effective in treating opioid and nicotine dependence; results from clinical studies suggest that the indirect dopamine agonist d-amphetamine may reduce cocaine abuse. In preclinical studies, chronic d-amphetamine treatment decreased ongoing cocaine self-administration.

Objectives

The present study extended previous results by determining effects of chronic d-amphetamine treatment on the reinforcing strength of cocaine under conditions in which access to cocaine was suspended during d-amphetamine treatment.

Methods

Daily operant conditioning sessions consisted of morning access to food pellets delivered under a 50-response fixed-ratio schedule and evening access to cocaine (0.005–0.48 mg/kg per injection, i.v.) under a progressive-ratio schedule. After responding maintained by 0.045 mg/kg per injection cocaine stabilized, self-administration sessions were suspended and d-amphetamine (0.01–0.1 mg/kg per hr, i.v.) was administered continuously for 5 days. On the following day, d-amphetamine treatment was discontinued and daily self-administration sessions resumed.

Results

Following termination of d-amphetamine treatment, food- and cocaine-maintained responding was decreased in a dose-related manner. Decreases in the reinforcing strength of cocaine were larger and lasted longer than effects on food reinforcement. However, cocaine self-administration was unaltered if 6 days elapsed between discontinuation of d-amphetamine treatment and the next cocaine self-administration session.

Conclusions

The necessity of a self-administration session in the presence of d-amphetamine suggests that the protracted decrease in cocaine self-administration may be a manifestation of behavioral tolerance. Regarding treatment of cocaine dependence, data suggest that prolonged d-amphetamine treatment may be necessary to produce a sustained reduction in the reinforcing effects of cocaine.

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Acknowledgements

The authors thank Tonya Calhoun and Susan Nader for their assistance in completing these studies. This research was supported by NIDA grant P50 DA-06634. The authors have no conflicts of interest to declare.

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Authors and Affiliations

  1. Department of Physiology and Pharmacology, Center for the Neurobiology of Addiction Treatments (CNAT), Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC, 27157-1083, USA

    Paul W. Czoty, Jennifer L. Martelle & Michael A. Nader

  2. Department of Radiology, Center for the Neurobiology of Addiction Treatments (CNAT), Wake Forest University School of Medicine, Winston-Salem, NC, 27157-1083, USA

    Michael A. Nader

Authors
  1. Paul W. Czoty
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  2. Jennifer L. Martelle
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  3. Michael A. Nader
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Correspondence to Michael A. Nader.

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Czoty, P.W., Martelle, J.L. & Nader, M.A. Effects of chronic d-amphetamine administration on the reinforcing strength of cocaine in rhesus monkeys. Psychopharmacology 209, 375–382 (2010). https://doi.org/10.1007/s00213-010-1807-x

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  • DOI: https://doi.org/10.1007/s00213-010-1807-x

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