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The selective dopamine D3 receptor antagonists SB-277011A and NGB 2904 and the putative partial D3 receptor agonist BP-897 attenuate methamphetamine-enhanced brain stimulation reward in rats

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Abstract

Rationale

We have previously reported that selective antagonism of brain D3 receptors by SB-277011A or NGB 2904 significantly attenuates cocaine- or nicotine-enhanced brain stimulation reward (BSR).

Objective

In the present study, we investigated whether the selective D3 receptor antagonists SB-277011A and NGB 2904 and the putative partial D3 agonist BP-897 similarly reduce methamphetamine (METH)-enhanced BSR.

Materials and methods

Rats were trained to respond for rewarding electrical self-stimulation of the medial forebrain bundle. To assess the degree of drug-induced changes in BSR, a rate–frequency curve shift paradigm was used to measure brain-reward threshold (θ 0).

Results

METH (0.1–0.65 mg/kg, i.p.) dose-dependently lowered (∼10–50%) BSR thresholds, producing an enhancement of BSR. Pretreatment with SB-277011A (12 mg/kg, but not 24 mg/kg, i.p.) significantly attenuated METH-enhanced BSR. NGB 2904 (0.1–1.0 mg/kg, but not 10 mg/kg) also attenuated METH-enhanced BSR. SB-277011A or NGB 2904 alone, at the doses tested, had no effect on BSR. Pretreatment with BP-897 (0.1–5 mg/kg) dose-dependently attenuated METH-enhanced BSR. However, when the dose was increased to 10 mg/kg, BP-897 shifted the stimulation–response curve to the right (inhibited BSR itself) in the presence or absence of METH.

Conclusions

Selective antagonism of D3 receptors by SB-277011A or NGB 2904 attenuates METH-enhanced BSR in rats, while the METH-enhanced BSR attenuation produced by BP-897 may involve both D3 and non-D3 receptors. These findings support a potential use of selective D3 receptor antagonists for the treatment of METH addiction.

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Acknowledgment

This research was supported entirely by the Intramural Research Program of the National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services.

Conflict of interest statement

All authors hereby declare that, except for income received from their respective primary employers, no financial support or compensation has been received from any individual or corporate entity over the past 3 years for research or professional services. There are no personal financial holdings that could be perceived as constituting a potential conflict of interest.

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Authors and Affiliations

  1. Intramural Research Program, National Institute on Drug Abuse, Baltimore, MD, USA

    Krista Spiller, Zheng-Xiong Xi, Xiao-Qing Peng, Amy H. Newman & Eliot L. Gardner

  2. Department of Pharmaceutical Sciences, Saint John’s University, Jamaica, NY, USA

    Charles R. Ashby Jr.

  3. Psychiatry Centre of Excellence for Drug Discovery, GlaxoSmithKline Pharmaceuticals, Verona, Italy

    Christian Heidbreder

  4. MegaPharma Kft., Budapest, Hungary

    József Gaál

Authors
  1. Krista Spiller
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  2. Zheng-Xiong Xi
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  3. Xiao-Qing Peng
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  4. Amy H. Newman
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  5. Charles R. Ashby Jr.
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  8. Eliot L. Gardner
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Correspondence to Zheng-Xiong Xi.

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Spiller, K., Xi, ZX., Peng, XQ. et al. The selective dopamine D3 receptor antagonists SB-277011A and NGB 2904 and the putative partial D3 receptor agonist BP-897 attenuate methamphetamine-enhanced brain stimulation reward in rats. Psychopharmacology 196, 533–542 (2008). https://doi.org/10.1007/s00213-007-0986-6

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  • DOI: https://doi.org/10.1007/s00213-007-0986-6

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