title: Genetic variability in morphine sensitivity and tolerance between different strains of rats.
abstract: The development of tolerance, the sensitivity to morphine and the effective morphine plasma concentrations have been studied in Sprague-Dawley (SD-U) and Wistar (W) rats. Daily administration of morphine (10 mg/kg/12 h for 9 days) in W rats produced a reduction in morphine antinociception from day 1 (12+/-0 s) to day 9 (6.7+/-1. 9 s). Morphine antinociception in the SD-U rats did not change over the period of treatment. Naloxone abolished the antinociception of morphine in both opiate naive and chronically treated SD-U rats. The pharmacokinetic parameters of morphine and morphine-3-glucuronide did not differ significantly between strains. Both naive and chronically treated SD-U rats required smaller doses of morphine than W rats to obtain a maximum antinociceptive effect. Plasma concentrations following administration of the same dose of morphine, did not differ between strains or days of treatment. The range of morphine concentrations required to obtain a maximum effect were lower in SD-U rats, both on day 1 and day 8 when compared to W rats. These results show differences between the two strains with regard to both morphine sensitivity and development of tolerance, whilst also suggesting that the differences do not have a kinetic basis.
authors.affiliation: Instituto de Neurociencias and Departamento de Farmacologia y Terapéutica, Universidad Miguel Hernandez, C.S.I.C., Campus de San Juan, 03550, Alicante, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Mas
authors.forename: E
authors.initials: E
authors.lastname: Sabater
authors.forename: M J
authors.initials: MJ
authors.lastname: Olaso
authors.forename: J F
authors.initials: JF
authors.lastname: Horga
authors.forename: C C
authors.initials: CC
authors.lastname: Faura
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance / Q000235:genetics* / Q000502:physiology*; D008297:Male; D009020:Morphine / Q000493:pharmacokinetics*; D009022:Morphine Derivatives / Q000097:blood; D009619:Nociceptors / Q000187:drug effects / Q000378:metabolism; D010146:Pain / Q000188:drug therapy; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D013997:Time Factors
chemical_list: D009022:Morphine Derivatives; D009020:Morphine; C018108:morphine-3-glucuronide