Cocaine and Other Indirect-Acting Monoamine Agonists Differentially Attenuate a Naltrexone Discriminative Stimulus in Morphine-Treated Rhesus Monkeys

Lance R. McMahon, Stacy L. Sell, Charles P. France

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Monoaminergic drugs can modify opioid withdrawal in nonhumans, and cocaine is reported to attenuate opioid withdrawal in humans. Drug discrimination was used to examine whether s.c. cocaine or other indirect-acting monoamine agonists attenuate morphine (3.2 mg/kg/day) withdrawal induced by naltrexone and by 27 h of morphine deprivation. Naltrexone-precipitated withdrawal was attenuated not only by morphine but also by cocaine, amphetamine, and imipramine. However, reversal of naltrexone-precipitated withdrawal was greater for morphine than for any of the indirect-acting monoamine agonists. Attenuation of the naltrexone discriminative stimulus by indirect-acting monoamine agonists was pharmacologically selective insofar as drugs lacking affinity for monoamine transporters (ketamine and triazolam) were without effect. Twenty-seven hours of morphine deprivation occasioned naltrexone-lever responding and decreased response rate, and both effects were reversed by morphine, cocaine, and amphetamine and not by imipramine, desipramine, ketamine, and triazolam. Thus, indirect-acting monoamine agonists attenuate some (e.g., discriminative) aspects of naltrexone-precipitated withdrawal, whereas only indirect-acting agonists with high affinity for dopamine transporters attenuate deprivation-induced withdrawal. These results suggest that dopamine is differentially involved in naltrexone-and deprivation-induced withdrawal and support the notion that opioid-dependent individuals use stimulants, in part, to attenuate withdrawal.

Original languageEnglish (US)
Pages (from-to)111-119
Number of pages9
JournalJournal of Pharmacology and Experimental Therapeutics
Issue number1
StatePublished - Jan 1 2004


ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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