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Effects of pramipexole on the reinforcing effectiveness of stimuli that were previously paired with cocaine reinforcement in rats

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Abstract

Rationale

Dopamine D2-like agonists maintain responding when substituted for cocaine in laboratory animals. However, these effects appear to be mediated by an interaction with stimuli that were previously paired with cocaine reinforcement (CS).

Objectives

To evaluate the extent to which the pramipexole-maintained and pramipexole-induced responding are influenced by cocaine-paired stimuli.

Methods

Rats were trained to nosepoke for cocaine under fixed ratio 1 (FR1) or progressive ratio (PR) schedules of reinforcement. In FR1-trained rats, pramipexole was substituted for cocaine with injections either paired with CSs, or delivered in their absence. The capacity of experimenter-administered pramipexole to induce FR1 and PR responding for CS presentation was evaluated. The effects of altering stimulus conditions, as well as pretreatments with D2- (l-741,626) and D3-preferring (PG01037) antagonists on pramipexole-induced PR responding were also evaluated.

Results

When substituted for cocaine, pramipexole maintained responding at high rates when injections were paired with CSs, but low rates when CSs were omitted. Similarly, experimenter-administered pramipexole induced dose-dependent increases in FR1 or PR responding, with high rates of responding observed when the CS was presented, and low rates of responding when CS presentation was omitted. D2 and D3 antagonists differentially affected pramipexole-induced PR responding, with l-741,626 and PG01037 producing rightward, and downward shifts in the dose–response curve for CS-maintained responding, respectively.

Conclusions

These data indicate that pramipexole is capable of enhancing the reinforcing effectiveness of conditioned stimuli, and raise the possibility that similar mechanisms are responsible for the increased occurrence of impulse control disorders in patients being treated with pramipexole.

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Acknowledgement

This research was supported by NIDA grants DA 024897, DA 020669, as well as the NIDA-IRP.

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Authors and Affiliations

  1. Department of Pharmacology, University of Michigan Medical School, 1301 MSRB III, 1150 W. Medical Center Drive, Ann Arbor, MI, 48109–0632, USA

    Gregory T. Collins, Alyssa R. Cunningham, Shaomeng Wang & James H. Woods

  2. Departments of Internal Medicine and Medicinal Chemistry, University of Michigan Medical School, Ann Arbor, MI, 48109–0934, USA

    Jianyong Chen & Shaomeng Wang

  3. Medicinal Chemistry Section, National Institutes on Drug Abuse–Intramural Research Program, National Institutes of Health, 333 Cassell Drive, Baltimore, MD, 21224–0180, USA

    Amy H. Newman

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  1. Gregory T. Collins
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Correspondence to Gregory T. Collins.

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Collins, G.T., Cunningham, A.R., Chen, J. et al. Effects of pramipexole on the reinforcing effectiveness of stimuli that were previously paired with cocaine reinforcement in rats. Psychopharmacology 219, 123–135 (2012). https://doi.org/10.1007/s00213-011-2382-5

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  • DOI: https://doi.org/10.1007/s00213-011-2382-5

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