title: Daily mirfentanil induces (cross-) tolerance to the rate-decreasing effects of morphine and not mirfentanil.
abstract: The fentanyl derivative mirfentanil has a novel set of behavioral effects in non-humans including low-efficacy opioid actions and non-opioid antinociceptive actions. This study evaluated the rate-decreasing effects of mirfentanil, morphine, naltrexone and ketamine in pigeons both prior to and during a period of chronic treatment with mirfentanil (3.2-17.8 mg/kg/day). Daily treatment with mirfentanil did not modify the rate-decreasing effects of mirfentanil or ketamine; however, daily treatment decreased sensitivity to the rate-decreasing effects of morphine and increased sensitivity to naltrexone. These results demonstrate a lack of tolerance to an apparently non-opioid action (rate-decreasing effect) of mirfentanil, which might predict a lack of tolerance to the non-opioid antinociceptive actions of this compound. These results further indicate that cross-tolerance (to morphine) and dependence (increased sensitivity to naltrexone) can occur in the absence of tolerance (to mirfentanil).
authors.affiliation: Department of Pharmacology, Louisiana State University Medical Center, New Orleans 70112-1393, USA.
authors.forename: C A
authors.initials: CA
authors.lastname: Gauthier
authors.forename: J R
authors.initials: JR
authors.lastname: Bagley
authors.forename: L L
authors.initials: LL
authors.lastname: Brockunier
authors.forename: C P
authors.initials: CP
authors.lastname: France
mesh_terms: D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001143:Arousal / Q000187:drug effects*; D010856:Columbidae; D003216:Conditioning, Operant / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004361:Drug Tolerance; D005283:Fentanyl / Q000031:analogs & derivatives* / Q000494:pharmacology; D007649:Ketamine / Q000494:pharmacology; D009020:Morphine / Q000494:pharmacology*; D009271:Naltrexone / Q000494:pharmacology
chemical_list: D000700:Analgesics; D009271:Naltrexone; D007649:Ketamine; D009020:Morphine; C069209:mirfentanil; D005283:Fentanyl