Antagonism of the discriminative stimulus effects of (+)-7-OH-DPAT by remoxipride but not PNU-99194A

April J. Christian, Amy K. Goodwin, Lisa E. Baker

Research output: Contribution to journalArticlepeer-review

Abstract

The dopamine (DA) agonist 7-hydroxy-N,N-di-n-propyl-2-amino-tetralin (7-OH-DPAT) has been used extensively as a tool to investigate the role of DA D3 receptors in the reinforcing and discriminative stimulus properties of psychostimulant drugs. The present study examined the relative importance of D3 vs. D2 receptor actions in the discriminative stimulus effects of (+)-7-OH-DPAT (0.03 mg/kg, sc) in 16 male Sprague-Dawley rats trained to discriminate this compound from saline in a two-lever, water-reinforced operant procedure under a FR 20 schedule. Stimulus generalization and antagonism tests were conducted with cocaine and with various selective D2 and D3 receptor ligands. In contrast to previous findings that (+)-7-OH-DPAT substitutes for cocaine, the present results demonstrated that cocaine does not produce stimulus generalization in animals trained to discriminate (+)-7-OH-DPAT. Although two D3-preferring agonists, PD-128907 and pramipexole, produced complete stimulus generalization to the training drug, two highly selective D3 antagonists (PNU-99194A, PD 152255) failed to block the discriminative stimulus effects of (+)-7-OH-DPAT. However, the D2 antagonist remoxipride (3.0 mg/kg) produced a rightward shift in the (+)-7-OH-DPAT dose-response curve. These findings suggest that D2 receptors are critically involved in mediating the cue properties of (+)-7-OH-DPAT. However, alternative interpretations that PNU-99194A is not entirely D3 receptor selective should also be considered.

Original languageEnglish (US)
Pages (from-to)371-377
Number of pages7
JournalPharmacology Biochemistry and Behavior
Volume68
Issue number3
DOIs
StatePublished - May 29 2001

Keywords

  • (+)-7-OH-DPAT
  • D2 receptors
  • D3 receptors
  • Drug discrimination
  • PNU-99194A
  • Rats
  • Remoxipride

ASJC Scopus subject areas

  • Biochemistry
  • Toxicology
  • Pharmacology
  • Clinical Biochemistry
  • Biological Psychiatry
  • Behavioral Neuroscience

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