The rate-decreasing effects of fentanyl derivatives in pigeons before, during and after chronic morphine treatment

Cheryl A. Gauthier, Lisa R. Gerak, Jerome R. Bagley, L. L. Brockunier, Charles P. France

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Mirfentanil is a fentanyl derivative with non-opioid actions, including non-opioid antinociceptive effects in rhesus monkeys. The current study examined the rate-altering effects of mirfentanil and several other compounds in pigeons to assess: 1) the opioid and non-opioid actions of acutely-administered fentanyl derivatives; and 2) the development of cross-tolerance between each of these compounds and morphine. Seven pigeons responded under a fixed-ratio 20 (FR20) schedule of food delivery. In untreated pigeons, fentanyl, morphine, naltrexone, ketamine and three fentanyl derivatives (mirfentanil, OHM3463 and 0HM3295) decreased rates of key pecking in a dose-related manner. Naltrexone (0.1-1.0 mg/kg) attenuated the effects of OHM3463 and not mirfentanil or OHM3295, suggesting non-opioid mediation of the rate-decreasing effects for the latter two fentanyl derivatives. Subjects were treated daily with morphine for 9 weeks, up to a dose of 100 mg/kg per day, during which time the dose-effect curves for morphine, fentanyl and OHM3463 shifted rightward 6-, 10- and 2-fold, respectively, indicating the development of tolerance to morphine and cross-tolerance to fentanyl and OHM3463. Dose-effect curves for ketamine, OHM3295 and mirfentanil were not shifted to the right during morphine treatment, and the dose-effect curve for naltrexone was shifted leftward 180-fold. To the extent that rate-decreasing effects are predictive of antinociceptive effects, these data suggest that some fentanyl derivatives might be useful therapeutics under conditions where tolerance develops to morphine-like opioids.

Original languageEnglish (US)
Pages (from-to)67-73
Number of pages7
JournalPsychopharmacology
Volume137
Issue number1
DOIs
Publication statusPublished - May 28 1998

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Keywords

  • Cross-tolerance
  • Dependence
  • Fentanyl
  • Mirfentanil
  • Morphine
  • Non-opioid
  • OHM3295
  • OHM3463
  • Opioid
  • Tolerance

ASJC Scopus subject areas

  • Pharmacology

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