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

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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.

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Acknowledgements

This research was supported by NIH grants P01-DA14528, T32-DA07252, and P01-AT002038. Ms. Lauren M. Pepe was supported in part by Boston University’s Undergraduate Research Opportunities Program. All procedures were carried out in accordance with the Guidelines for the Care and Use of Mammals in Neuroscience and Behavioral Research (National Research Council 2003). We thank Justin Hamilton for expert technical assistance.

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Authors and Affiliations

  1. Alcohol and Drug Abuse Research Center, McLean Hospital/Harvard Medical School, 115 Mill Street, Belmont, MA, 02478, USA

    Morgane Thomsen, Lauren M. Pepe & S. Barak Caine

  2. Laboratory of Neuropsychiatry, Rigshospitalet University Hospital, 9 Blegdamsvej, 2100, Copenhagen, Denmark

    Anders Fink-Jensen, David P. D. Woldbye & Gitta Wörtwein

  3. Department of Neuroscience and Pharmacology, University of Copenhagen, 9 Blegdamsvej, 2100, Copenhagen, Denmark

    Anders Fink-Jensen, David P. D. Woldbye & Gitta Wörtwein

  4. Division of Neurobiology, H. Lundbeck A/S, 9 Ottiliavej, 2500, Valby, Denmark

    Thomas N. Sager

  5. Preformulation, H. Lundbeck A/S, 9 Ottiliavej, 2500, Valby, Denmark

    Rene Holm

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  1. Morgane Thomsen
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  2. Anders Fink-Jensen
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  3. David P. D. Woldbye
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  4. Gitta Wörtwein
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Correspondence to Morgane Thomsen.

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Thomsen, M., Fink-Jensen, A., Woldbye, D.P.D. et al. Effects of acute and chronic aripiprazole treatment on choice between cocaine self-administration and food under a concurrent schedule of reinforcement in rats. Psychopharmacology 201, 43–53 (2008). https://doi.org/10.1007/s00213-008-1245-1

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  • DOI: https://doi.org/10.1007/s00213-008-1245-1

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