Genetic variability in morphine sensitivity and tolerance between different strains of rats |
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Authors: | Mas M Sabater E Olaso M J Horga J F Faura C C |
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Affiliation: | Instituto de Neurociencias and Departamento de Farmacologia y Terapéutica, Universidad Miguel Hernandez, C.S.I.C., Campus de San Juan, 03550, Alicante, Spain. |
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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. |
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Keywords: | Morphine Genetic variability Sensitivity Tolerance Pharmacokinetics Rats |
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