title: Effects of 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM) and quipazine on heroin self-administration in rhesus monkeys.
abstract: BACKGROUND
  The serotonin (5-HT) system is involved in pain modulation, and 5-HT receptor agonists can enhance antinociceptive effects of mu opioid receptor agonists. Less is known about the actions of 5-HT receptor agonists on other effects of opioids.
  
  
  OBJECTIVE
  This study examined the effects of non-contingent and contingent administration of the 5-HT(2A) receptor agonists DOM and quipazine on i.v. heroin self-administration in rhesus monkeys.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Pharmacology, The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX, USA.
authors: David R
authors: DR
authors: Maguire
authors: Jun-Xu
authors: JX
authors: Li
authors: Wouter
authors: W
authors: Koek
authors: Charles P
authors: CP
authors: France
mesh_terms: D004290:DOM 2,5-Dimethoxy-4-Methylamphetamine / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D003932:Heroin / Q000008:administration & dosage*; D008253:Macaca mulatta; D008297:Male; D011814:Quipazine / Q000008:administration & dosage / Q000494:pharmacology*; D012055:Reinforcement Schedule; D012646:Self Administration; D058826:Serotonin 5-HT2 Receptor Agonists / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D058826:Serotonin 5-HT2 Receptor Agonists; D004290:DOM 2,5-Dimethoxy-4-Methylamphetamine; D011814:Quipazine; D003932:Heroin