Acute administration of SB-277011A, NGB 2904, or BP 897 inhibits cocaine cue-induced reinstatement of drug-seeking behavior in rats: role of dopamine D3 receptors

Synapse. 2005 Jul;57(1):17-28. doi: 10.1002/syn.20152.


Recent studies have shown that the novel dopamine (DA) D3 receptor antagonists SB-277011A and NGB 2904 inhibit cocaine- and/or stress-induced reinstatement of drug-seeking behavior. The present study sought to determine if SB-277011A, NGB 2904, or BP-897 (a mixed D3 agonist/antagonist) similarly inhibit cocaine-associated cue-induced reinstatement of drug-seeking behavior. Long-Evans rats were allowed to self-administer cocaine. Each cocaine infusion was paired with discrete conditioned cue-light and tone. Subsequently, drug-seeking (i.e., lever-pressing) behavior was extinguished in the absence of cocaine and cocaine-associated cues. Rats were then tested for cue-induced reinstatement of drug-seeking. We found that cocaine-associated cues evoked robust reinstatement of lever-pressing. Acute intraperitoneal (i.p.) administration of SB-277011A (6, 12, or 24 mg/kg) produced a dose-dependent inhibition of cue-induced reinstatement of drug-seeking behavior by 35, 65, and 85%, respectively, compared to vehicle-treated animals. Acute i.p. administration of NGB 2904 (0.1, 1.0, or 5.0 mg/kg) produced a 45, 30, and 70% inhibition of cue-induced reinstatement, respectively, compared to vehicle-treated animals. Acute i.p. administration of either 0.1 or 1 mg/kg of BP 897 did not produce a significant effect on cue-induced reinstatement, whereas a dose of 3 mg/kg produced a 70% inhibition of cue-induced reinstatement. These findings, combined with previous data, suggest that DA D3 receptor antagonism may underlie the inhibitory effects of SB-277011A and NGB 2904 on cocaine cue-induced reinstatement, while the effects of BP 897 may involve D3 and non-D3 receptor mechanisms.

MeSH terms

  • Animals
  • Cocaine / antagonists & inhibitors*
  • Cocaine / pharmacology
  • Cocaine-Related Disorders / drug therapy
  • Cocaine-Related Disorders / psychology*
  • Conditioning, Operant / drug effects
  • Cues*
  • Dopamine Antagonists / pharmacology*
  • Dopamine D2 Receptor Antagonists*
  • Extinction, Psychological / drug effects
  • Fluorenes / pharmacology*
  • Male
  • Nitriles / pharmacology*
  • Photic Stimulation
  • Piperazines / pharmacology*
  • Rats
  • Rats, Long-Evans
  • Receptors, Dopamine D3
  • Recurrence
  • Self Administration
  • Tetrahydroisoquinolines / pharmacology*


  • Dopamine Antagonists
  • Dopamine D2 Receptor Antagonists
  • Drd3 protein, rat
  • Fluorenes
  • NGB 2904
  • Nitriles
  • Piperazines
  • Receptors, Dopamine D3
  • SB 277011
  • Tetrahydroisoquinolines
  • BP 897
  • Cocaine