The dopamine D3 receptor antagonist PNU-99194A fails to block (+)-7-OH-DPAT substitution for D-amphetamine or cocaine

Lisa E. Baker, Kjell A. Svensson, Kelly J. Garner, Amy K. Goodwin

Research output: Contribution to journalArticlepeer-review

Abstract

The present study examined the role of dopamine D3 receptor actions in the stimulus generalization produced by (+)-7-OH-DPAT in rats trained to discriminate either d-amphetamine or cocaine from saline. Twelve male Sprague-Dawley rats were trained to discriminate d-amphetamine (1.0 mg/kg) and 12 rats were trained to discriminate cocaine (5.0 mg/kg) from saline in a two-choice, water-reinforced operant procedure. Stimulus generalization tests were administered with the D3 receptor-preferring agonist, (+)-7-hydroxy-N,N-di-n-propyl-2-aminotetralin ((+)-7-OH-DPAT, 0.01-1.0 mg/kg) as well as the D3-preferring antagonist, 5,6-di-methoxy-2-(dipropylamino)indan-hydrochloride (PNU-99194A, 5-40 mg/kg). PNU-99194A (10-40 mg/kg) was also administered in combination with the training dose of d-amphetamine or cocaine to test for antagonism of each training drug cue. Finally, to assess the role of D3 receptor actions in the stimulus generalization produced by (+)-7-OH-DPAT (0.1 mg/kg), PNU-99194A (10, 20 mg/kg) was tested in combination with this compound in each training group. The results showed complete stimulus generalization with (+)-7-OH-DPAT in rats trained to discriminate d-amphetamine, although only partial stimulus generalization was observed with this compound in rats trained to discriminate cocaine. PNU-99194A produced partial substitution for both training drugs, and failed to block the discriminative stimulus effects of either d-amphetamine or cocaine. Moreover, this compound failed to block the stimulus generalization produced by (+)-7-OH-DPAT in rats trained to discriminate d-amphetamine. These results question the importance of D3 receptor actions in the discriminative stimulus effects of psychostimulants and their similarities to (+)-7-OH-DPAT. Copyright (C) 1998 Elsevier Science B.V.

Original languageEnglish (US)
Pages (from-to)101-109
Number of pages9
JournalEuropean Journal of Pharmacology
Volume358
Issue number2
DOIs
StatePublished - Oct 2 1998

Keywords

  • (+)-7-OH-DPAT
  • Cocaine
  • D-Amphetamine
  • Dopamine D receptor
  • Drug discrimination
  • PNU-99194A

ASJC Scopus subject areas

  • Pharmacology

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