The effects of nociceptin/orphanin FQ receptor agonist Ro 64-6198 and diazepam on antinociception and remifentanil self-administration in rhesus monkeys

Christopher A. Podlesnik, Mei Chuan Ko, Gail Winger, Jürgen Wichmann, Eric P. Prinssen, James H. Woods

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

Rationale: The synthetic nonpeptide NOP (nociceptin/orphanin FQ peptide) receptor agonist Ro 64-6198 produces antinociception in rhesus monkeys. In rodents, it has much more variable effects on pain responses, but has response rate-increasing effects on punished operant behavior and decreases drug reward. Objectives: The aim of this study was to compare Ro 64-6198 with the benzodiazepine diazepam in tests of analgesia, drug self-administration, and response-increasing effects in rhesus monkeys. Results: Ro 64-6198 (0.001-0.01 mg/kg, i.v.) produced antinociception against an acute noxious stimulus (50°C water) in the absence of sedation, whereas diazepam (0.32-3.2 mg/kg, i.v.) did not have analgesic effects without sedation. Diazepam (1.0-5.6 mg/kg, i.v.) and the largest dose of Ro 64-6198 (0.32 mg/kg, i.v.) decreased lever pressing maintained by intravenous self-administration of the mu-opioid agonist, remifentanil, but neither effect could be distinguished from sedative effects. Although neither drug consistently increased responding during nonreinforcement, such effects were observed more frequently following diazepam administration. The effects of Ro 64-6198 on lever pressing were blocked by the NOP-receptor antagonist, J-113397, but not by the benzodiazepine antagonist, flumazenil. Conclusions: These findings suggest that the effects of Ro 64-6198 on operant lever pressing are mediated by NOP receptors and that larger doses are required to impact operant behavior when compared directly with those that produce antinociception. Therefore, the present findings support previous literature suggesting NOP receptors are a viable target for pain management.

Original languageEnglish (US)
Pages (from-to)53-60
Number of pages8
JournalPsychopharmacology
Volume213
Issue number1
DOIs
StatePublished - Jan 2011
Externally publishedYes

Keywords

  • Antinociception
  • Benzodiazepine
  • Diazepam
  • Flumazenil
  • J-113397
  • NOP receptor
  • Remifentanil
  • Rhesus monkey
  • Ro 64-6198
  • Self-administration

ASJC Scopus subject areas

  • Pharmacology

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