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Effects of repeated treatment with the dopamine D2/D3 receptor partial agonist aripiprazole on striatal D2/D3 receptor availability in monkeys

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Abstract

Rationale

Chronic treatment with dopamine (DA) receptor agonists and antagonists can differentially affect measures of DA D2/D3 receptor number and function, but the effects of chronic treatment with a partial D2/D3 receptor agonist are not clear.

Objective

We used a within-subjects design in male cynomolgus monkeys to determine the effects of repeated (17-day) treatment with the D2/D3 receptor partial agonist aripiprazole (ARI; 0.03 mg/kg and 0.1 mg/kg i.m.) on food-reinforced behavior (n = 5) and on D2/D3 receptor availability as measured with positron emission tomography (PET; n = 9).

Methods

Five monkeys responded under a fixed-ratio 50 schedule of food reinforcement and D2/D3 receptor availability was measured before and 4 days after ARI treatment using PET and the D2/D3 receptor-selective radioligand [18F]fluoroclebopride (FCP). Four additional monkeys were studied using [11C]raclopride and treated sequentially with each dose of ARI for 17 days.

Results

ARI decreased food-maintained responding with minimal evidence of tolerance. Repeated ARI administration increased FCP and raclopride distribution volume ratios (DVRs) in the caudate nucleus and putamen in most monkeys, but decreases were observed in monkeys with the highest baseline DVRs.

Conclusions

The results indicate that repeated treatment with a low-efficacy DA receptor partial agonist produces effects on brain D2/D3 receptor availability that are qualitatively different from those of both high-efficacy receptor agonists and antagonists, and suggest that the observed individual differences in response to ARI treatment may reflect its partial agonist activity.

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Acknowledgments

This research was supported by the National Institute on Drug Abuse (DA 10584, DA 12460 and DA 14637). The authors thank Michael Coller, Michelle Icenhower Bell, and Michael Bounds for their assistance in conducting these experiments.

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Authors and Affiliations

  1. Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC, 27157-1083, USA

    Paul W. Czoty & Michael A. Nader

  2. Department of Radiology, Wake Forest University School of Medicine, Winston-Salem, NC, 27157, USA

    H. Donald Gage, Pradeep K. Garg, Sudha Garg & Michael A. Nader

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  1. Paul W. Czoty
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  2. H. Donald Gage
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  3. Pradeep K. Garg
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  4. Sudha Garg
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  5. Michael A. Nader
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Correspondence to Michael A. Nader.

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Czoty, P.W., Gage, H.D., Garg, P.K. et al. Effects of repeated treatment with the dopamine D2/D3 receptor partial agonist aripiprazole on striatal D2/D3 receptor availability in monkeys. Psychopharmacology 231, 613–619 (2014). https://doi.org/10.1007/s00213-013-3274-7

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  • DOI: https://doi.org/10.1007/s00213-013-3274-7

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