, Volume 231, Issue 5, pp 949–954

Reduction of the reinforcing effectiveness of cocaine by continuous d-amphetamine treatment in rats: importance of active self-administration during treatment period

  • Benjamin A. Zimmer
  • Keri A. Chiodo
  • David C. S. Roberts
Original Investigation



Continuous administration of d-amphetamine has shown promise as a treatment for psychostimulant addiction. In rodent studies, constant infusion of d-amphetamine (5 mg/kg/day) has been shown to reduce cocaine-reinforced responding in the dose range of 0.19–0.75 mg/kg/inf.


The present study tested whether these effects were a reflection of pharmacological interactions between d-amphetamine and cocaine or if they resulted from associative learning mechanisms


After stable progressive ratio (PR) baselines were established, rats were implanted with subcutaneous osmotic minipumps filled with either d-amphetamine (5 mg/kg/day—groups 1 and 2) or saline (group 3). During the treatment period, groups 1 and 3 self-administered cocaine at a dose that was previously shown to produce the most robust effects in combination with d-amphetamine treatment (0.19 mg/kg/inf), while group 2 received passive cocaine infusions.


In replication of previous studies, d-amphetamine treatment resulted in a significant (35 %) decrease in breakpoints relative to saline controls. By contrast, no reductions in breakpoints were observed in animals that received passive cocaine infusions during the treatment period (group 2).


Active self-administration of cocaine during the treatment period appears to be an important factor in reducing cocaine-reinforced breakpoints. These findings suggest learning mechanisms are involved in the therapeutic effects of continuous d-amphetamine, and pharmacological interaction mechanisms such as cross-tolerance cannot completely account for the observed decreases in cocaine seeking.


Addiction Agonist therapy Breakpoint Cocaine d-amphetamine Dose Progressive ratio Rat Reinforcing efficacy Self-administration 


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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Benjamin A. Zimmer
    • 1
    • 2
  • Keri A. Chiodo
    • 1
    • 2
  • David C. S. Roberts
    • 1
  1. 1.Department of Physiology and PharmacologyWake Forest University Health SciencesWinston-SalemUSA
  2. 2.Neuroscience ProgramWake Forest University Health SciencesWinston-SalemUSA

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