Effects of the putative dopamine autoreceptor antagonists (+)-AJ 76 and (+)-UH 232 on the discriminative stimulus properties of cocaine

Patrick M. Callahan, Montford F. Piercey, Kathryn A. Cunningham

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Abstract

Recent evidence suggests that the putative dopamine (DA) autoreceptor antagonists, (+)-AJ 76 and (+)-UH 232, share some neurochemical and behavioral effects with both psychostimulants and neuroleptics. The ability of (+)-AJ 76 and (+)-UH 232 to mimic or antagonize the stimulus effects of cocaine was investigated in rats trained to discriminate 5 mg/kg (N=8) or 10 mg/kg (N=8) of cocaine from saline in a two-lever, water-reinforced, drug discrimination task. In the cocaine (10 mg/kg) group, administration of (+)-AJ 76 (2.5-20 mg/kg) engendered only a partial substitution for cocaine (maximum 60% cocaine-lever responses). Given in combination with cocaine (10 mg/kg), (+)-AJ 76 (2.5-40 mg/kg) did not significantly attenuate the cocaine cue. A fixed dose of (+)-AJ 76 (2.5 or 10 mg/kg) plus various doses of cocaine (1.25-5 mg/kg) did not alter the cocaine dose-response curve. (+)-UH 232 (2-16 mg/kg) produced primarily saline-appropriate responding in rats trained to discriminate 5 mg/kg of cocaine and was unable to block the interoceptive cocaine state when given in combination with cocaine (5 mg/kg). (+)-UH 232 (2 or 8 mg/kg) also did not alter the cocaine dose-response curve. These results suggest that (+)-AJ 76 and (+)-UH 232 elicit only weak or no cocaine-like stimulus effects and, unlike neuroleptics, do not attenuate the cocaine cue.

Original languageEnglish (US)
Pages (from-to)73-77
Number of pages5
JournalPsychopharmacology
Volume107
Issue number1
DOIs
StatePublished - May 1 1992

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Keywords

  • (+)-AJ 76
  • (+)-UH 232
  • Cocaine
  • Dopamine autoreceptor
  • Drug discrimination

ASJC Scopus subject areas

  • Pharmacology

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