, Volume 196, Issue 4, pp 533–542

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

  • Krista Spiller
  • Zheng-Xiong Xi
  • Xiao-Qing Peng
  • Amy H. Newman
  • Charles R. AshbyJr.
  • Christian Heidbreder
  • József Gaál
  • Eliot L. Gardner
Original Investigation



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).


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 (θ0).


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.


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.


Methamphetamine Dopamine D3 receptor Brain reward SB-277011A NGB 2904 BP-897 


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Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Krista Spiller
    • 1
  • Zheng-Xiong Xi
    • 1
  • Xiao-Qing Peng
    • 1
  • Amy H. Newman
    • 1
  • Charles R. AshbyJr.
    • 2
  • Christian Heidbreder
    • 3
  • József Gaál
    • 4
  • Eliot L. Gardner
    • 1
  1. 1.Intramural Research ProgramNational Institute on Drug AbuseBaltimoreUSA
  2. 2.Department of Pharmaceutical SciencesSaint John’s UniversityJamaicaUSA
  3. 3.Psychiatry Centre of Excellence for Drug DiscoveryGlaxoSmithKline PharmaceuticalsVeronaItaly
  4. 4.MegaPharma Kft.BudapestHungary

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