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  • Title: A selective kappa-opioid agonist, U-50,488H, blocks the development of tolerance to morphine analgesia in rats.
    Author: Yamamoto T, Ohno M, Ueki S.
    Journal: Eur J Pharmacol; 1988 Oct 26; 156(1):173-6. PubMed ID: 2850208.
    Abstract:
    The development of tolerance to morphine analgesia was completely blocked by the coadministration of a selective kappa-opioid agonist, U-50,488H at doses of 3.2 or 10 mg/kg i.p. These doses of U-50,488H exerted no analgesic effect by themselves and did not affect the analgesia induced by 10 mg/kg of morphine. The analgesic effect of morphine was restored when 10 mg/kg of U-50,488H was coinjected in morphine-tolerant rats. These findings suggest that activation of the kappa-opioid system prevents the development of tolerance to morphine analgesia.
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