Psychopharmacology

, Volume 201, Issue 1, pp 43–53

Effects of acute and chronic aripiprazole treatment on choice between cocaine self-administration and food under a concurrent schedule of reinforcement in rats

  • Morgane Thomsen
  • Anders Fink-Jensen
  • David P. D. Woldbye
  • Gitta Wörtwein
  • Thomas N. Sager
  • Rene Holm
  • Lauren M. Pepe
  • S. Barak Caine
Original Investigation

Abstract

Rationale

Dopamine D2-like partial agonists such as aripiprazole have received some attention as potential pharmacotherapies for the treatment of psychostimulant addiction. However, the preclinical evaluations so far have focused on acute effects of aripiprazole.

Objectives

We tested the hypothesis that aripiprazole, both as acute and as chronic treatment, would preferentially decrease cocaine self-administration while sparing behavior maintained by a natural reinforcer, resulting in a shift in the allocation of behavior from cocaine-taking towards the alternative reinforcer.

Materials and methods

Rats were trained to self-administer intravenous cocaine in a concurrent choice procedure, with a palatable food as the competing reinforcer, under a fixed ratio (FR) 1 FR 5 chain schedule. Aripiprazole was then administered as continuous infusion by osmotic minipumps for 5 days, during which performance in the choice procedure was assessed daily.

Results

An intermediate dose of aripiprazole decreased cocaine self-administration and shifted the cocaine choice curve to the right as an acute treatment. However, as a chronic treatment, aripiprazole failed to decrease cocaine self-administration or cocaine choice, despite a dose-dependent decrease in overall response rates and food-maintained behavior.

Conclusions

Our results confirm and extend earlier findings and indicate that acute administration of aripiprazole can decrease cocaine self-administration. However, based on the present data, chronic treatment with aripiprazole does not show much promise as a potential pharmacotherapy for cocaine addiction. Both acute and chronic treatment data are in agreement with published clinical findings, suggesting that the concurrent choice procedure in rats has predictive validity of efficacy in humans.

Keywords

Self-administration Cocaine Concurrent choice schedule Chronic treatment Partial agonist 

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Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Morgane Thomsen
    • 1
  • Anders Fink-Jensen
    • 2
    • 3
  • David P. D. Woldbye
    • 2
    • 3
  • Gitta Wörtwein
    • 2
    • 3
  • Thomas N. Sager
    • 4
  • Rene Holm
    • 5
  • Lauren M. Pepe
    • 1
  • S. Barak Caine
    • 1
  1. 1.Alcohol and Drug Abuse Research CenterMcLean Hospital/Harvard Medical SchoolBelmontUSA
  2. 2.Laboratory of NeuropsychiatryRigshospitalet University HospitalCopenhagenDenmark
  3. 3.Department of Neuroscience and PharmacologyUniversity of CopenhagenCopenhagenDenmark
  4. 4.Division of NeurobiologyH. Lundbeck A/SValbyDenmark
  5. 5.Preformulation, H. Lundbeck A/SValbyDenmark

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