Cocaine and other indirect-acting monoamine agonists differentially attenuate a naltrexone discriminative stimulus in morphine-treated rhesus monkeys.
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.
McMahon
Lance R
LR
Department of Pharmacology, The University of Texas Health Science Center, San Antonio, Texas 78229-3900, USA.
Sell
Stacy L
SL
France
Charles P
CP
D000661:Amphetamine / Q000627:therapeutic use; D000818:Animals; D015306:Biogenic Monoamines / Q000819:agonists; D003042:Cocaine / Q000627:therapeutic use*; D004193:Discrimination Learning / Q000187:drug effects*; D004195:Disease Models, Animal; D015259:Dopamine Agents / Q000627:therapeutic use*; D018765:Dopamine Uptake Inhibitors / Q000627:therapeutic use; D004347:Drug Interactions; D007099:Imipramine / Q000627:therapeutic use; D008253:Macaca mulatta; D009020:Morphine / Q000009:adverse effects*; D009021:Morphine Dependence; D009271:Naltrexone / Q000494:pharmacology*; D009294:Narcotics / Q000009:adverse effects; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy*
D015306:Biogenic Monoamines; D015259:Dopamine Agents; D018765:Dopamine Uptake Inhibitors; D009294:Narcotics; D009271:Naltrexone; D009020:Morphine; D000661:Amphetamine; D003042:Cocaine; D007099:Imipramine