Abstract | RATIONALE: OBJECTIVE: RESULTS:
Heroin (0.0001-0.1 mg/kg/infusion) generated an inverted U-shaped dose-response function. Non-contingent administration of DOM (0.1-0.32 mg/kg) flattened the dose-response function in three monkeys and eliminated heroin self-administration in a fourth monkey. Contingent DOM (0.0032-0.032 mg/kg/infusion) alone did not maintain responding above that maintained by saline, and, when added to self-administered heroin, monkeys responded less than for the same unit doses of heroin alone. Non-contingent (0.32-3.2 mg/kg) and contingent (0.0032-0.56 mg/kg/infusion) administration of quipazine flattened the dose-response function in two monkeys, increasing responding maintained by small unit doses of heroin and saline, but failed to enhance responding for heroin in two other monkeys. CONCLUSION: This study shows that DOM does not enhance, and might attenuate, the positive reinforcing effects of the mu opioid receptor agonist heroin. Quipazine increased responding for saline and small doses of heroin; those effects were modest and observed in only two subjects. Taken together, these data suggest that 5-HT(2A) receptor agonists do not significantly enhance the reinforcing effectiveness of mu opioid receptor agonists and support the view that administering 5-HT drugs in combination with opioids to treat pain might not enhance abuse liability.
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Authors | David R Maguire, Jun-Xu Li, Wouter Koek, Charles P France |
Journal | Psychopharmacology
(Psychopharmacology (Berl))
Vol. 225
Issue 1
Pg. 173-85
(Jan 2013)
ISSN: 1432-2072 [Electronic] Germany |
PMID | 22836370
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Chemical References |
- Serotonin 5-HT2 Receptor Agonists
- DOM 2,5-Dimethoxy-4-Methylamphetamine
- Quipazine
- Heroin
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Topics |
- DOM 2,5-Dimethoxy-4-Methylamphetamine
(administration & dosage, pharmacology)
- Animals
- Dose-Response Relationship, Drug
- Female
- Heroin
(administration & dosage)
- Macaca mulatta
- Male
- Quipazine
(administration & dosage, pharmacology)
- Reinforcement Schedule
- Self Administration
- Serotonin 5-HT2 Receptor Agonists
(administration & dosage, pharmacology)
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