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

• Published in: Psychopharmacologia Vol. 137; no. 1; pp. 67 - 73
• Main Authors: Gauthier, Cheryl A., Gerak, Lisa R., Bagley, Jerome R., Brockunier, L. L., France, C. P.
• Format: Journal Article
• Language: English
• Published: Berlin Springer 01.05.1998; Springer Nature B.V
• Subjects: Analgesics; Analgesics - pharmacology; Animals; Biological and medical sciences; Birds; Columbidae; Conditioning (Psychology) - drug effects; Cross-tolerance; Dose-Response Relationship, Drug; Drug Tolerance; Fentanyl; Fentanyl - analogs & derivatives; Fentanyl - pharmacology; Ketamine; Medical sciences; Morphine; Morphine - pharmacology; Naltrexone; Naltrexone - pharmacology; Narcotics; Neuropharmacology; Opioids; Pain perception; Pharmacology. Drug treatments; Tolerance; Instrumental conditioning; Morphine; Opiates; Narcotic analgesic; Pigeon; Learning; Vertebrata; Acquisition process; Analgesic; Animal; Dependence; Cross reaction; Aves; Mirfentanil
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s002130050594

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 OHM3295) 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.