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 Citations (Scopus)

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
StatePublished - 1998
Externally publishedYes

Fingerprint

Columbidae
Fentanyl
Morphine
Naltrexone
Ketamine
Opioid Analgesics
Macaca mulatta
Appointments and Schedules
mirfentanil
Food

Keywords

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

ASJC Scopus subject areas

  • Pharmacology

Cite this

The rate-decreasing effects of fentanyl derivatives in pigeons before, during and after chronic morphine treatment. / Gauthier, Cheryl A.; Gerak, Lisa R; Bagley, Jerome R.; Brockunier, L. L.; France, Charles P.

In: Psychopharmacology, Vol. 137, No. 1, 1998, p. 67-73.

Research output: Contribution to journalArticle

Gauthier, Cheryl A. ; Gerak, Lisa R ; Bagley, Jerome R. ; Brockunier, L. L. ; France, Charles P. / The rate-decreasing effects of fentanyl derivatives in pigeons before, during and after chronic morphine treatment. In: Psychopharmacology. 1998 ; Vol. 137, No. 1. pp. 67-73.
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